Details of the Researcher

PHOTO

Nobuo Fuse
Section
Tohoku Medical Megabank Organization
Job title
Professor
Degree

Education 3

  • Tohoku University　Graduate School, Division of Medicine　Ophthalmology

    - 1997/03

  • Tohoku University　Faculty of Medicine

    - 1991/03/31

  • 山形県立山形東高等学校

    - 1984/03

Committee Memberships 1

  • 日本緑内障学会　評議員

    - Present

Research Interests 3

  • ゲノム科学

  • 人類遺伝学

  • 眼科学

Research Areas 4

  • Life sciences / Genomics /

  • Life sciences / Medical biochemistry /

  • Life sciences / Healthcare management, medical sociology /

  • Life sciences / Ophthalmology /

Awards 7

  1. 加藤記念難病研究助成基金賞

    2014

  2. 日本眼科学会評議員会賞

    2013/04　日本眼科学会

  3. 宮城県医師会奨学賞金賞

    2010/01

  4. 東北大学医学部奨学賞金賞

    2010/01　東北大学　テーラーメード医療に向けた緑内障の原因遺伝子・感受性遺伝子の分子遺伝学的解析

  5. 須田記念緑内障治療研究奨励基金賞

    2008/09　日本眼科学会　テーラーメード医療のための緑内障原因遺伝子・感受性遺伝子の解析

  6. 今井記念緑内障研究助成金賞

    2007/09　日本眼科学会　オーダーメード医療を目指した緑内障原因遺伝子・感受性遺伝子の解析

  7. 海外研究助成賞

    1999　日本眼球銀行協会

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Papers 241

  1. Significant Correlation Between White Matter Hyperintensity Volume and Rare NOTCH3 Variants in the General Japanese Population.

    Ikuko Mizuta, Fumio Yamashita, Yoichi Sutoh, Atsushi Shimizu, Akiko Watanabe-Hosomi, Yayoi Otsuka-Yamasaki, Shunji Mugikura, Kengo Kinoshita, Makiko Taira, Naoko Mori, Akiko Miyazawa, Hiraku Matsuura, Tomo Saito, Hiroshi Sakamoto, Masayuki Yamamoto, Makoto Sasaki, Nobuo Fuse, Toshiki Mizuno

    Geriatrics & gerontology international　26　(2)　e70400　2026/02

    DOI： 10.1111/ggi.70400 　

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    AIM: Cerebral small vessel disease (CSVD)-related MRI findings, including white matter hyperintensities (WMHs), are not rare in general elderly populations. The aim of this study was to elucidate the contribution of hereditary CSVD-related genes to CSVD-related MRI findings in a general Japanese population. METHODS: We analyzed datasets from 324 individuals aged ≥ 50 years in Tohoku Medical Megabank (TMM), focusing on MRI markers and variants of NOTCH3, ABCC6, COL4A1, COL4A2, GLA, HTRA1, and TREX1 genes. Background factors included age, sex, hypertension, diabetes, dyslipidemia, hyperuricemia, alcohol drinking, and smoking. RESULTS: Pathogenic variant carriers were identified within ABCC6 (n = 20), but not other genes. To compare with previous studies including rare NOTCH3 variants regardless of pathogenicity, we included 24 rare functional variants of NOTCH3. We performed a gene-based analysis using the burden test and sequence kernel association test (SKAT) adjusted for background factors, between WMH/lacune and ABCC6/NOTCH3. The only significant finding was the correlation between WMH volume and rare NOTCH3 variants by SKAT, both with the basic model, adjusted for age, sex, and hypertension (p = 0.045), and full model, adjusted for all background factors (p = 0.027). We also analyzed the association between intracranial major artery stenosis/occlusion (ICASO) and RNF213 p.Arg4810Lys, the East Asian-specific variant susceptible to ICASO; however, we failed to identify a significant correlation. CONCLUSIONS: This study suggests that NOTCH3 may contribute to WMH volume in a general Japanese population.

  2. Distribution of axial length in Japanese children and adolescents aged 4 to 19 years.

    Shunsuke Fujioka, Naoko Takada, Sayaka Yoshida, Mami Ishikuro, Masayuki Kobayashi, Genki Shinoda, Aoi Noda, Masatsugu Orui, Taku Obara, Satoru Tsuda, Noriko Himori, Akiko Hanyuda, Ryo Kawasaki, Shinichi Kuriyama, Nobuo Fuse, Toru Nakazawa

    Japanese journal of ophthalmology　2026/01/19

    DOI： 10.1007/s10384-026-01328-1 　

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    PURPOSE: To investigate the distribution of axial length (AL) and the prevalence of long axial length (LAL) in Japanese children and adolescents. STUDY DESIGN: cross-sectional observational study METHODS: We analyzed AL data from 14,482 participants (7,457 boys and 7,025 girls) aged 4-19 in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. AL was measured using a non-contact optical axis measurement device. We evaluated the distribution of AL in the participants with box plots for age. Segmented regression identified age-related trends and breakpoints. We calculated the age-specific proportions of participants with AL ≥ 24.5 mm and those with AL ≥ 26 mm, defined as LAL, which were considered indicative of suspected myopia. RESULTS: Mean AL increased with age, with a break point at 11.73 years. The slope before the break point was β = 0.27, while the slope after the break point decreased to β = 0.12. Boys showed earlier break point (9.87 years) than girls (15.91 years). Proportions with AL ≥ 24.5mm and ≥26mm began to increase approximately at 8 and 10 years of age respectively, with sex differences noted between ages 7 to 10 years and 10 to 11 years. CONCLUSION: This was the first large-scale AL survey in Japan and revealed the age and sex related distribution of AL and the proportion with LAL among Japanese children and adolescents aged 4 to 19 years.

  3. Establishment of Ascertainment Methods for Cardiovascular Disease Onset in the Tohoku Medical Megabank Organization

    Rieko Hatanaka, Naoki Nakaya, Sayuri Tokioka, Ippei Chiba, Taku Obara, Hirohito Metoki, Masahiro Kikuya, Kotaro Nochioka, Masatsugu Orui, Kai Susukita, Masato Takase, Ikumi Kanno, Mana Kogure, Kumi Nakaya, Mami Ishikuro, Satoshi Nagaie, Soichi Ogishima, Yohei Hamanaka, Eiichi N. Kodama, Nobuo Fuse, Shinichi Kuriyama, Atsuhi Hozawa

    Circulation Reports　2025/12/26

    Publisher: Japanese Circulation Society

    DOI： 10.1253/circrep.cr-25-0263 　

    eISSN： 2434-0790

  4. Relationship between age-related hearing loss and alcohol consumption in a Japanese population. International-journal

    Hiyori Takahashi, Jun Suzuki, Ikuko N Motoike, Miyuki Sakurai, Yuta Kobayashi, Gosuke Watarai, Hiroki Tozuka, Mana Kogure, Tetsuaki Kawase, Yohei Honkura, Ryoukichi Ikeda, Kengo Kinoshita, Naoki Nakaya, Taku Obara, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto, Yukio Katori

    Scientific reports　16　(1)　336-336　2025/12/02

    DOI： 10.1038/s41598-025-29634-7 　

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    Age-related hearing loss (ARHL) has a multifactorial pathogenesis, and the influence of alcohol consumption on it is controversial. This cross-sectional study investigated the association between ARHL and alcohol consumption by using cohort data from Tohoku Medical Megabank Project, including self-reported questionnaires and pure-tone audiometry thresholds (500, 1000, 2000, and 4000 Hz). ARHL was defined as a threshold of > 25 dB in the better ear. Multiple logistic regression analyses (age 50-79 y; 5,219 men and 9,266 women) were conducted separately for men and women and indicated that daily alcohol consumption levels of 60-80 and ≥ 80 g were significantly associated with increased odds of ARHL at 4,000 Hz in men (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.05-1.94; OR 1.55; 95% CI 1.12-2.16; respectively); consumption of 10-20 g was significantly associated with reduced odds of ARHL at 4,000 Hz in women (OR 0.81; 95% CI 0.68-0.96). Assessment of drinking-related single nucleotide polymorphisms suggested that the effect of alcohol on ARHL may differ by genotype. Our findings suggest a sex-specific association between alcohol consumption and ARHL; heavy drinking is a potential risk factor in men, whereas moderate drinking may have a protective effect in women.

  5. Population attributable fraction of all-cause mortality due to non-normal blood pressure: results from the 2013 to 2016 baseline survey of the TMM CommCohort Study. International-journal

    Rieko Hatanaka, Naoki Nakaya, Mana Kogure, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Masato Takase, Yuka Kotozaki, Taku Obara, Satoshi Nagaie, Hideki Ohmomo, Takahito Nasu, Michihiro Satoh, Takahisa Murakami, Hirohito Metoki, Yohei Hamanaka, Masatsugu Orui, Eiichi N Kodama, Nobuo Fuse, Yoko Izumi, Kozo Tanno, Atsushi Hozawa

    Hypertension research : official journal of the Japanese Society of Hypertension　2025/11/12

    DOI： 10.1038/s41440-025-02436-0 　

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    Antihypertensive therapy has reduced cardiovascular mortality; however, challenges remain, including residual risk in treated patients and the population burden associated with borderline hypertension. Previous Japanese estimates of the population attributable fraction (PAF) are derived from older cohorts and often lacked stratification by treatment status. We conducted a prospective study of 61,495 participants (women: 56.7%, aged 60.7 ± 11.0 years) from the Tohoku Medical Megabank Community-Based Cohort Study. Participants were classified into six blood pressure (BP) categories based on the JSH 2019 guidelines, and further stratified by hypertension treatment status, resulting in 12 groups. Using untreated individuals with normal BP as the reference, we calculated multivariable-adjusted hazard ratios (HR), 95% confidence intervals (CI), and PAF for the remaining groups using Cox proportional hazards model. During a median follow-up of 6.5 years, 1909 deaths were recorded. HRs increased with rising BP in both untreated and treated participants. The overall PAF for all-cause mortality due to non-normal BP was 9.45%, with a marked sex difference (12.25% in male and 5.16% in female). The highest PAF contributions were observed in the treated Grade I hypertension group (2.18%) and the untreated elevated BP group (1.28%). In this contemporary Japanese cohort, non-normal BP accounts for 9.45% of all-cause mortality, representing a substantial public health burden, particularly among men. The substantial PAF contributions from both treated patients and untreated individuals with elevated BP highlight the importance of effective BP management for both primary and secondary prevention.

  6. Advancements in Whole-Genome Sequencing Protocols: A Decade of In-House Operations and Quality Controls at the Tohoku Medical Megabank.

    Fumiki Katsuoka, Junko Kawashima, Shu Tadaka, Akihito Otsuki, Yasunobu Okamura, Takafumi Suzuki, Takanori Hidaka, Kazuki Kumada, Fuji Nagami, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto

    JMA journal　8　(4)　1039-1052　2025/10/15

    DOI： 10.31662/jmaj.2025-0159 　

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    Population-scale human whole-genome sequencing (WGS) projects are ongoing worldwide. At a time when such large-scale genome projects were uncommon, the Tohoku Medical Megabank Project initiated genome analysis of the general population in Japan, aiming to build a foundation for personalized medicine and prevention. Recently, we have completed the WGS of 100,000 participants, and research utilizing this genomic foundation is in progress. Early in the project, we realized that standard protocols were not always suitable for large-scale sequencing, necessitating the development of optimized operations and quality control methods. To accommodate various sequencing platforms and adapt protocols to the scale of analysis, we have continuously refined our methods. As multiplex sequencing analysis became standard, we aimed to ensure uniform data quantity across samples. With the advent of large-scale analyses, streamlining operations has also been a critical focus. In this paper, we share the details of our WGS operations and quality control methods developed over a decade, highlighting the unique methods and know-how we have established.

  7. Associations of family history of hypertension, genetic, and lifestyle risks with incident hypertension. International-journal

    Masato Takase, Takumi Hirata, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Kotaro Nochioka, Tomohiro Nakamura, Naho Tsuchiya, Hirohito Metoki, Michihiro Satoh, Akira Narita, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Ippei Takahashi, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

    Hypertension research : official journal of the Japanese Society of Hypertension　48　(10)　2606-2617　2025/10

    DOI： 10.1038/s41440-025-02314-9 　

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    Family history of hypertension may reflect genetic and lifestyle factors. Genetic risk can be assessed using polygenic risk score (PRS); however, whether PRS can stratify hypertension risk when combined with family history and lifestyle information is unclear. This prospective cohort study included 9,001 hypertension-free individuals aged ≥20 years from the Tohoku Medical Megabank Community-Based Cohort Study. Participants were scored on lifestyle factors, including body mass index, urinary sodium-to-potassium ratio, physical activity, alcohol consumption, and smoking at recruitment. During the mean follow-up of 4.3 years, 2822 (31.4%) cases of hypertension occurred. High genetic risk and poor lifestyle were associated with increased hypertension risk. Compared with participants with low genetic risk, ideal lifestyle, and no family history, high genetic risk significantly increased hypertension risk, even among those with ideal lifestyle and no family history (relative risk [RR] 1.28 [95% confidence interval [CI] 1.11-1.46]). Participants with low PRS, ideal lifestyle, but with family history had increased hypertension risk (RR 1.32 [95%CI 1.11-1.57]). Poor lifestyle increased hypertension risk across most genetic risk groups, regardless of family history. Integrating PRS into models with family history and lifestyle risk significantly improved predictive accuracy (area under the curve: 0.671 for family history and lifestyle risk and 0.674 for PRS integrated; P for difference <0.05). Integrating PRS with lifestyle and family history enhances the stratification of individuals at high risk for hypertension.

  8. Genome-Wide Association Study of Cognitive Function in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study. International-journal

    Genki Shinoda, Taku Obara, Ippei Takahashi, Hisashi Ohseto, Chikana Kawaguchi, Akira Narita, Aoi Noda, Keiko Murakami, Masatsugu Orui, Mami Ishikuro, Makiko Taira, Hiroshi Sakamoto, Naoki Nakaya, Atsushi Hozawa, Nobuo Fuse, Gen Tamiya, Shunji Mugikura, Kyoko Suzuki, Shinichi Kuriyama

    Genes, brain, and behavior　24　(5)　e70038　2025/10

    DOI： 10.1111/gbb.70038 　

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    Heritability of cognitive function is estimated to be 50%-80%. Genome-wide association studies (GWASs) have identified multiple cognitive function-associated loci, primarily in the European population. However, those in Asian populations, particularly in individuals of Japanese ancestry, remain limited. Hence, this GWAS aimed to identify cognitive function-associated genetic loci in elderly individuals of Japanese ancestry. Herein, 2571 elderly participants from the Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study were included. Their cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE), and both binary and continuous MMSE scores were analysed. Genotyping was performed using the Affymetrix Axiom Japonica Array v2, and imputation was conducted with 3.5KJPNv2 and 1KGP3. Statistical analyses were performed using FastGWA-GLMM and FastGWA for binary and continuous MMSE scores, respectively. Although no genome-wide significant loci were identified using binary MMSE values, the following two were detected using continuous MMSE values: rs77877360 (20p12.1) near BANF2 and SNX5 and rs9460729 (6p22.3) near PRL and HDGFL1. Additionally, functional annotation suggested the involvement of these loci in pathways related to cognitive function, including chromatin structure regulation, neuroinflammation, and iron metabolism. Notably, SNX5, identified through chromatin-interaction mapping, has been implicated in neurodegenerative processes, particularly in Parkinson's disease. The findings of this study provide preliminary genome-wide evidence suggesting a genetic predisposition to impaired cognitive function in elderly Japanese individuals.

  9. Effect of healthy lifestyle on renal dysfunction risk: interactions with genetic risk. International-journal

    Masato Takase, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Kotaro Nochioka, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Ikumi Kanno, Akira Narita, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Ippei Takahashi, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Koichi Matsuda, Yoko Izumi, Kengo Kinoshita, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

    Clinical kidney journal　18　(10)　sfaf275　2025/10

    DOI： 10.1093/ckj/sfaf275 　

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    BACKGROUND: Whether adherence to a healthy lifestyle can mitigate genetic risk for renal dysfunction remains unclear. METHODS: This prospective cohort study included 12 680 adults aged ≥20 years, free from chronic kidney disease at baseline, enrolled in the Tohoku Medical Megabank Community-based Cohort study. A healthy lifestyle score-based on normal weight, never smoking, never drinking, regular physical activity, and a low urinary sodium-to-potassium ratio-classified participants into ideal, intermediate, or poor lifestyle groups. A polygenic risk score (PRS) was constructed using estimated glomerular filtration rate (eGFR) data from a previous multi-ancestry genome-wide association meta-analysis. The primary outcome was renal dysfunction, defined as eGFR <60.0 ml/min/1.73 m2. RESULTS: Among the 12 680 adults, 123 participants (0.9%) developed renal dysfunction during a mean follow-up of 4.4 ± 0.8 years. Poor lifestyle was consistently associated with higher risk of renal dysfunction across most PRS categories. Participants with intermediate genetic risk had elevated risk only when also exhibiting an intermediate lifestyle. Formal testing for effect modification by PRS provided modest evidence that the association between high genetic risk and increased risk of renal dysfunction was stronger among individuals with an intermediate lifestyle. Although the addition of the PRS to the model included the C-statistic, this improvement was not statistically significant. CONCLUSIONS: Maintaining a healthy lifestyle is associated with lower risk of renal dysfunction, regardless of genetic risk. Combining PRSs with lifestyle information may enhance risk stratification, although further studies are needed to improve predictive accuracy.

  10. Exploring risk factors for axial length elongation: a population-based cohort study of 9195 eyes in Japan. International-journal

    Takayuki Nishimura, Hiroshi Kunikata, Naoko Takada, Makoto Ishikawa, Sayuri Tokioka, Rieko Hatanaka, Mana Kogure, Ippei Chiba, Kumi Nakaya, Taku Obara, Yoko Izumi, Akira Uruno, Satoshi Nagaie, Soichi Ogishima, Naoki Nakaya, Shinichi Kuriyama, Atsushi Hozawa, Nobuo Fuse, Toru Nakazawa

    The British journal of ophthalmology　2025/09/15

    DOI： 10.1136/bjo-2025-327213 　

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    PURPOSE: To investigate long-term axial length (AL) changes in adults and to identify risk factors contributing to excessive AL elongation, which is associated with high myopia, we analysed a large dataset of adults without ocular pathology from the Tohoku Medical Megabank Project Community-based Cohort Study in Japan. METHODS: We conducted a longitudinal investigation of 9195 participants aged ≥20 years with several years of follow-up (mean 3.5 years). Based on the upper quartile of AL elongation for people aged in their 20s, we defined AL elongation exceeding 0.033 mm per year as high AL elongation (HALE). We used multiple logistic regression analyses to assess potential risk factors for HALE. RESULTS: A longitudinal investigation revealed that AL can fluctuate and even become elongated during adulthood, particularly among middle-aged and older individuals. Notably, HALE occurred in 618 out of 9195 eyes (6.7%). The proportion in each age group, comprising people aged in their 20s, 30s, 40s, 50s, 60s, 70s and 80s, was 24.7%, 12.7%, 9.4%, 5.2%, 4.5%, 4.0% and 1.4%, respectively. In addition, we also observed that younger age (OR 1.45 per 10 years older), female gender (OR 1.63), high myopia (OR 2.74) and serum immunoglobulin E (IgE) levels >171 IU/mL (OR 1.27) were associated with HALE. CONCLUSION: Findings from a large prospective cohort study confirmed that in Japanese individuals, HALE was significantly associated with high serum IgE levels, as well as with younger age, female gender and pre-existing high myopia.

  11. Cohort Profile Update: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study) 2023 update. International-journal

    Taku Obara, Mami Ishikuro, Aoi Noda, Keiko Murakami, Masatsugu Orui, Genki Shinoda, Fumihiko Ueno, Fumiko Matsuzaki, Tomomi Onuma, Hiroko Matsubara, Hirohito Metoki, Masahiro Kikuya, Rieko Hatanaka, Ippei Chiba, Kumi Nakaya, Mana Kogure, Naoki Nakaya, Junichi Sugawara, Shigeo Kure, Mika Kobayashi, Tomoko Kobayashi, Yoichi Suzuki, Hiroshi Kawame, Mika Sakurai-Yageta, Sachiko Nagase, Naoki Nakamura, Tomohiro Nakamura, Satoshi Mizuno, Satoshi Nagaie, Soichi Ogishima, Akira Narita, Gen Tamiya, Sachie Koreeda, Fuji Nagami, Toru Tamahara, Maki Goto, Akihito Otsuki, Makiko Taira, Takanori Hidaka, Junko Kawashima, Eiichi N Kodama, Akira Uruno, Yohei Hamanaka, Hiroaki Tomita, Hiroaki Hashizume, Kenichi Noguchi, Fumiki Katsuoka, Seizo Koshiba, Kazuki Kumada, Takahiro Nobukuni, Kinuko Ohneda, Shunji Mugikura, Ritsuko Shimizu, Masataka Kambe, Yoshinobu Saito, Tadao Kobayashi, Yoko Izumi, Kengo Kinoshita, Nobuo Fuse, Nobuo Yaegashi, Atsushi Hozawa, Masayuki Yamamoto, Shinichi Kuriyama

    International journal of epidemiology　54　(5)　2025/08/18

    DOI： 10.1093/ije/dyaf148 　

  12. Association of circulating metabolites and polygenic risk score with incident type 2 diabetes: a prospective community-based cohort study. International-journal

    Masato Takase, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Kotaro Nochioka, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Seizo Koshiba, Kazuki Kumada, Ikuko Motoike, Eiji Hishinuma, Akira Narita, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Ippei Takahashi, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Koichi Matsuda, Yoko Izumi, Kinuko Ohneda, Kengo Kinoshita, Atsushi Hozawa, Masayuki Yamamoto

    Cardiovascular diabetology　24　(1)　335-335　2025/08/14

    DOI： 10.1186/s12933-025-02849-8 　

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    BACKGROUND: No previous studies have explored metabolites associated with both genetic predispositions to type 2 diabetes (T2DM) and T2DM onset. Therefore, we aimed to explore metabolic profiles using genetic risk to identify pathways for tailored T2DM prevention strategies. METHODS: This prospective community-based cohort study in Japan included a total of 12,461 participants aged ≥ 20 years. Genetic predictors were genome-wide and pathway-based polygenic risk scores (PRSs). We quantified 43 metabolites using nuclear magnetic resonance spectroscopy. T2DM was defined as a non-fasting glucose level of ≥ 200 mg/dL, glycated hemoglobin level ≥ 6.5%, or self-reported T2DM treatment. A modified Poisson regression model was used to examine the associations of PRSs and metabolites with T2DM incidence. Linear associations were tested using the restricted cubic spline, and mediation analysis was conducted to assess the mediating effect of metabolites on the association between PRSs and T2DM incidence. RESULTS: During the 4.3-year median follow-up period, 354 T2DM cases were identified. A higher PRS was associated with incident T2DM (relative risk [RR] 2.09, 95% confidence interval [CI], 1.68-2.60, P < 0.001, 1-standard deviation [SD] increment). The nitrogen compound transport pathway PRS was associated with incident T2DM (RR 1.32, 95% CI 1.03-1.70, P < 0.001, 1-SD increment). Fourteen metabolites like glucose, 2-ketoisocaproic acid, glutamic acid, leucine, 2-aminobutyric acid, 2-hydroxybutyric acid, valine, 3-methyl-2-oxobutyric acid, alanine, 3-hydroxybutyric acid, 3-methyl-2-oxiovaleric acid, formic acid, arginine, and tyrosine were positively associated with the risk of T2DM. Only glycine was inversely associated with the risk of T2DM. Among 43 metabolites, 14 metabolites were positively associated with PRS (P for linear trend < 0.05). 3-hydroxyisobutyric-acid, 2-Aminobutyric acid, 2-ketoisocaproic acid, 2-hydroxybutyric acid, leucine, glycine, and glucose mediated the association between PRS and incident T2DM. CONCLUSIONS: Several metabolites were found to mediate the association between PRS and incident T2DM. These findings may contribute to a better understanding of the metabolic pathways involved in genetic susceptibility to T2DM.

  13. Household income modifies the association between social capital and gestational diabetes mellitus in Japan: Results from TMM BirThree Cohort Study.

    Koichi Sakakibara, Tomoki Kawahara, Nobutoshi Nawa, Keiko Murakami, Hisashi Ohseto, Ippei Takahashi, Akira Narita, Taku Obara, Mami Ishikuro, Masatsugu Orui, Aoi Noda, Genki Shinoda, Satoshi Nagaie, Soichi Ogishima, Junichi Sugawara, Shigeo Kure, Kengo Kinoshita, Atsushi Hozawa, Nobuo Fuse, Gen Tamiya, Wendy L Bennett, Shinichi Kuriyama, Takeo Fujiwara, Pamela J Surkan

    Journal of diabetes investigation　2025/07/08

    DOI： 10.1111/jdi.70101 　

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    INTRODUCTION: While social capital can prevent diabetes, these benefits can be heterogeneous with respect to socioeconomic status. We investigated the association between social capital and gestational diabetes mellitus (GDM) while examining effect modification by household income. MATERIALS AND METHODS: We conducted a secondary data analysis using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study carried out between July 2013 and March 2017. Social capital (mutual aid, social trust, informal social control, collective action) and covariates were self-reported, while GDM diagnosis and other medical and physiological information were obtained from medical records. To assess the association between social capital and GDM, we conducted logistic regression models. We further tested for interactions between social capital and household income as well as stratified the models by income. RESULTS: Among 20,339 study participants, 700 (3.4%) were diagnosed with GDM. Multivariable logistic regression models found that social trust and collective action were associated with lower GDM prevalence, even after adjustment of covariates. When stratifying household income, however, social capital was significantly associated with the reduced risks of GDM only among participants with higher household income (OR: 0.90, 95% CI: 0.85-0.97). No significant association was observed among those with lower household income. CONCLUSIONS: The health benefit of social capital on GDM prevalence was heterogeneous, and the protective effect of social capital on GDM was found only among women with higher household income. The differential impact of social capital on GDM highlights the need for targeted interventions addressing structural health inequities.

  14. Gaze Patterns of Children with Communication Difficulties Associated with Core Symptoms of Autism Spectrum Disorder.

    Mika Kobayashi, Tomoko Kobayashi, Taku Obara, Akira Narita, Akimitsu Miyake, Tomohisa Suzuki, Mami Ishikuro, Masatsugu Orui, Eiichi N Kodama, Ritsuko Shimizu, Yohei Hamanaka, Yoko Izumi, Atsushi Hozawa, Nobuo Fuse, Atsuo Kikuchi, Gen Tamiya, Shigeo Kure, Shinichi Kuriyama, Masayuki Yamamoto

    The Tohoku journal of experimental medicine　2025/06/12

    DOI： 10.1620/tjem.2025.J074 　

  15. Association Between Sodium- and Potassium-Related Urinary Markers and the Prevalence of Atrial Fibrillation.

    Sayuri Tokioka, Naoki Nakaya, Rieko Hatanaka, Kumi Nakaya, Mana Kogure, Ippei Chiba, Masato Takase, Kotaro Nochioka, Kai Susukita, Hirohito Metoki, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Satoshi Nagaie, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Satoshi Yasuda, Atsushi Hozawa

    Circulation journal : official journal of the Japanese Circulation Society　89　(6)　757-764　2025/05/23

    DOI： 10.1253/circj.CJ-24-0780 　

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    BACKGROUND: The primary prevention of atrial fibrillation (AF), which increases mortality through complications including stroke and heart failure, is important. Excessive salt intake and low potassium intake are risk factors for cardiovascular disease; however, their association with AF remains inconclusive. This study investigated the association between sodium- and potassium-related urinary markers and AF prevalence. METHODS AND RESULTS: Data from the Tohoku Medical Megabank Project Community-based Cohort Study were used in this cross-sectional study. The urinary sodium-to-potassium (Na/K) ratio and estimated 24-h sodium and potassium excretion were calculated using spot urine samples and categorized into quartiles (Q1-Q4). The prevalence of AF was the primary outcome. Of the 26,506 participants (mean age 64.8 years; 33.2% males) included in this study, 630 (2.4%) had AF. Using Q1 as the reference group, the odds ratios for AF prevalence in Q4 were 1.35 (95% confidence interval [CI] 1.07-1.73) and 1.59 (95% CI 1.20-2.12) for 24-h estimated urinary Na/K ratio and estimated 24-h sodium excretion, respectively. Estimated 24-h potassium excretion was not associated with AF prevalence. CONCLUSIONS: AF prevalence was positively associated with the urinary Na/K ratio and estimated 24-h urinary sodium excretion, but not with estimated 24-h urinary potassium excretion. Although further prospective studies are warranted, the findings of this study suggest that salt intake may be a modifiable risk factor for AF.

  16. STAT image reporting in a large-scale cohort: types, frequency, and insights from the Tohoku Medical Megabank Brain MRI Study.

    Naoko Mori, Shunji Mugikura, Yuto Abe, Atsushi Hozawa, Nobuo Fuse, Masayuki Yamamoto

    Japanese journal of radiology　2025/05/15

    DOI： 10.1007/s11604-025-01800-x 　

  17. Integration of Digital Phenotyping and Genomics for Dry Eye Disease: Protocol for a Prospective Cohort Study. International-journal

    Ken Nagino, Yasutsugu Akasaki, Nobuo Fuse, Soichi Ogishima, Atsushi Shimizu, Akira Uruno, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Fuji Nagami, Jun Seita, Tomohiro Nakamura, Satoshi Nagaie, Makiko Taira, Tomoko Kobayashi, Ritsuko Shimizu, Atsushi Hozawa, Shinichi Kuriyama, Atsuko Eguchi, Akie Midorikawa-Inomata, Masahiro Nakamura, Akira Murakami, Shintaro Nakao, Takenori Inomata

    JMIR research protocols　14　e67862　2025/05/12

    DOI： 10.2196/67862 　

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    BACKGROUND: Dry eye disease (DED) is a common ocular condition with diverse and heterogeneous symptoms. Current treatment standards of DED include the post facto management of associated symptoms through topical eye drops. However, there is a need for predictive, preventive, personalized, and participatory medicine. The DryEyeRhythm mobile health app enables real-time data collection on environmental, lifestyle, host, and digital factors in a patient's daily environment. Combining these data with genetic information from biobanks could enhance our understanding of individual variations and facilitate the development of personalized treatment strategies for DED. OBJECTIVE: This study aims to integrate digital data from the DryEyeRhythm smartphone app with the Tohoku Medical Megabank database to create a comprehensive database that elucidates the interplay between multifactorial factors and the onset and progression of DED. METHODS: This prospective observational cohort study will include 1200 participants for the discovery stage and 1000 participants for the replication stage, all of whom have data available in the Tohoku Medical Megabank database. Participants will be recruited from the Community Support Center of Sendai, Miyagi Prefecture, Japan. Participant enrollment for the discovery stage was conducted from August 1, 2021, to June 30, 2022, and the replication stage will be conducted from August 31, 2024, to March 31, 2026. Participants will provide demographic data, medical history, lifestyle information, DED symptoms, and maximum blink interval measurements at baseline and after 30 days using the DryEyeRhythm smartphone app. Upon scanning a registration code, each participant's cohort ID from the Tohoku Medical Megabank database will be linked to their smartphone app, enabling data integration between the Tohoku Medical Megabank and DryEyeRhythm database. The primary outcome will assess the association between genetic polymorphisms and DED using a genome-wide association study. Secondary outcomes will explore associations between DED and various factors, including sociodemographic characteristics, lifestyle habits, medical history, biospecimen analyses (eg, blood and urine), and physiological measurements (eg, height, weight, and eye examination results). Associations will be evaluated using logistic regression analysis, adjusting for potential confounding factors. RESULTS: The discovery stage of participant enrollment was conducted from August 1, 2021, to June 30, 2022. The replication stage will take place from August 31, 2024, to March 31, 2026. Data analysis is expected to be completed by September 2026, with results reported by March 2027. CONCLUSIONS: This study highlights the potential of smartphone apps in advancing biobank research and deepening the understanding of multifactorial DED, paving the way for personalized treatment strategies in the future. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67862.

  18. 心血管疾患危険因子と大脳白質病変変化の関連 TMM計画地域住民コホート調査

    佐竹 芽久美, 千葉 一平, 中谷 直樹, 森 菜緒子, 布施 昇男, 木下 賢吾, 泉 陽子, 麦倉 俊司, 寳澤 篤

    日本老年医学会雑誌　62　(Suppl.)　172-172　2025/05

    Publisher: (一社)日本老年医学会

    ISSN： 0300-9173

  19. Concordance of Cancer Screening Attendance Among Spouse Couples: A Cross-Sectional Survey of the Tohoku Medical Megabank Project. International-journal

    Naoki Nakaya, Kumi Nakaya, Toshimasa Sone, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Sayuri Tokioka, Masato Takase, Yoko Izumi, Nobuo Fuse, Atsushi Hozawa

    Psycho-oncology　34　(5)　e70158　2025/05

    DOI： 10.1002/pon.70158 　

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    OBJECTIVES: Owing to spousal pairs often exhibiting similar health behaviors, this study examined the concordance of cancer screening attendance between spouses using cross-sectional data from a large biobank study in Japan, which included 2022 spousal pairs. STUDY DESIGN: Cross-sectional study. METHODS: Self-administered data were collected to determine whether participants had undergone screening for colorectal, gastric, and lung cancers in the past year. The following two analyses were conducted: the exposure was whether the husband attended cancer screening, and the outcome was whether the wife attended; the exposure was whether the wife attended, and the outcome was whether the husband attended. Multiple logistic regression analyses were performed, adjusting for confounding factors in the exposed individuals. RESULTS: The multivariate odds ratio (95% confidence interval, p-value) for wives attending colorectal cancer screening when their husbands had attended was 2.7 (2.2-3.3, p < 0.0001), indicating a significant positive association. Similarly, when wives were the exposure and husbands were the outcomes, the odds ratio was 2.6 (2.2-3.2, p < 0.0001). Notably, these associations were consistent across colorectal, gastric, and lung cancer screenings. CONCLUSIONS: The findings of this study support the hypothesis that the attendance of one spouse at cancer screening significantly positively influences that of the other spouse, regardless of the type of cancer screening or the age of the spouses. Novel intervention strategies can be developed that specifically target spousal pairs and potentially enhance the effectiveness of cancer prevention initiatives compared to those targeting individuals alone.

  20. Parental axial lengths and prenatal conditions related to child axial length: The TMM BirThree Cohort Study

    Mami Ishikuro, Nobuo Fuse, Taku Obara, Aoi Noda, Genki Shinoda, Masatsugu Orui, Akira Uruno, Sayaka Yoshida, Naoko Takada, Shunsuke Fujioka, Takayuki Nishimura, Akiko Hanyuda, Ryo Kawasaki, Toru Nakazawa, Shinichi Kuriyama

    AJO International　2　(1)　2025/04/28

    DOI： 10.1016/j.ajoint.2024.100088 　

    eISSN： 2950-2535

  21. Sex difference in genetic risk in the prevalence of atrial fibrillation. International-journal

    Sayuri Tokioka, Masato Takase, Naoki Nakaya, Rieko Hatanaka, Kumi Nakaya, Mana Kogure, Ippei Chiba, Kotaro Nochioka, Hirohito Metoki, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Satoshi Nagaie, Soichi Ogishima, Yoko Izumi, Gen Tamiya, Nobuo Fuse, Shinichi Kuriyama, Satoshi Yasuda, Atsushi Hozawa

    Heart rhythm　2025/03/23

    DOI： 10.1016/j.hrthm.2025.03.1974 　

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    BACKGROUND: Early detection and management of atrial fibrillation (AF) are crucial. Combined models incorporating genetic risks and clinical risks have been developed to improve predictive ability. Although sex differences have been reported in many aspects of AF, sex differences in genetic risk have not been studied. OBJECTIVE: The purpose of this study was to assess the sex difference in the effect of polygenic risk score for AF (AF-PRS) on AF prevalence using cross-sectional data from the Tohoku Medical Megabank Project Community-Based Cohort Study in Japan. METHODS: AF-PRS and Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation (CHARGE-AF) score were used for genetic AF risks and clinical AF risks, respectively. Sex differences in the association of AF-PRS with the prevalence of AF were evaluated. RESULTS: Among 16,853 participants (mean age 63.4 years; 5182, 30.7% men), the prevalence of AF was 255 (4.9%) in men and 130 (1.1%) in women. In the group with high AF-PRS and high CHARGE-AF score, the odds ratio for AF was highest in men and women (8.2 in men and 9.4 in women), compared with that in the group with low AF-PRS and low CHARGE-AF score. Integrating AF-PRS into the CHARGE-AF score significantly enhanced the area under the receiver operating characteristic curve for AF in men (from 0.639 to 0.749) but not in women (from 0.710 to 0.733). CONCLUSION: Our study is the first to show a sex difference in the association of AF-PRS and AF prevalence. AF-PRS is more closely associated with the prevalence of AF in men than in women.

  22. Genetic effects on gestational diabetes mellitus and their interactions with environmental factors among Japanese women

    Tomoki Kawahara, Nobutoshi Nawa, Keiko Murakami, Toshihiro Tanaka, Hisashi Ohseto, Ippei Takahashi, Akira Narita, Taku Obara, Mami Ishikuro, Masatsugu Orui, Aoi Noda, Genki Shinoda, Yuki Nagata, Satoshi Nagaie, Soichi Ogishima, Junichi Sugawara, Shigeo Kure, Kengo Kinoshita, Atsushi Hozawa, Nobuo Fuse, Gen Tamiya, Wendy L. Bennett, Margaret A. Taub, Pamela J. Surkan, Shinichi Kuriyama, Takeo Fujiwara

    Journal of Human Genetics　70　(5)　265-273　2025/03/21

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s10038-025-01330-4 　

    ISSN： 1434-5161

    eISSN： 1435-232X

  23. COPD 臨床 血中好酸球数とPRISm移行リスクの関連性 ToMMo地域住民コホート調査からの知見

    岩崎 史, 中谷 久美, 山田 充啓, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 千葉 一平, 高瀬 雅仁, 時岡 紗由里, 布施 昇男, 寳澤 篤, 杉浦 久敏

    日本呼吸器学会誌　14　(増刊)　162-162　2025/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  24. Returning genetic risk information for hereditary cancers to participants in a population-based cohort study in Japan. International-journal

    Kinuko Ohneda, Yoichi Suzuki, Yohei Hamanaka, Shu Tadaka, Muneaki Shimada, Junko Hasegawa-Minato, Masanobu Takahashi, Nobuo Fuse, Fuji Nagami, Hiroshi Kawame, Tomoko Kobayashi, Yumi Yamaguchi-Kabata, Kengo Kinoshita, Tomohiro Nakamura, Soichi Ogishima, Kazuki Kumada, Hisaaki Kudo, Shin-Ichi Kuriyama, Yoko Izumi, Ritsuko Shimizu, Mikako Tochigi, Tokiwa Motonari, Hideki Tokunaga, Atsuo Kikuchi, Atsushi Masamune, Yoko Aoki, Chikashi Ishioka, Takanori Ishida, Masayuki Yamamoto

    Journal of human genetics　2025/01/17

    DOI： 10.1038/s10038-024-01314-w 　

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    Large-scale population cohort studies that collect genomic information are tasked with returning an assessment of genetic risk for hereditary cancers to participants. While several studies have applied to return identified genetic risks to participants, comprehensive surveys of participants' understanding, feelings, and behaviors toward cancer risk remain to be conducted. Here, we report our experience and surveys of returning genetic risks to 100 carriers of pathogenic variants for hereditary cancers identified through whole genome sequencing of 50 000 individuals from the Tohoku Medical Megabank project, a population cohort study. The participants were carriers of pathogenic variants associated with either hereditary breast and ovarian cancer (n = 79, median age=41) or Lynch syndrome (n = 21, median age=62). Of these, 28% and 38% had a history of cancer, respectively. We provided information on cancer risk, heritability, and clinical actionability to the participants in person. The comprehension assessment revealed that the information was better understood by younger (under 60 years) females than by older males. Scores on the cancer worry scale were positively related to cancer experiences and general psychological distress. Seventy-one participants were followed up at Tohoku University Hospital; six females underwent risk-reducing surgery triggered by study participation and three were newly diagnosed with cancer during surveillance. Among first-degree relatives of hereditary breast and ovarian cancer carriers, participants most commonly shared the information with daughters. This study showed the benefits of returning genetic risks to the general population and will provide insights into returning genetic risks to asymptomatic pathogenic variant carriers in both clinical and research settings.

  25. Language Registration-Based Scoring System for Handwritten Logical Memory of Wechsler Memory Scale-Revised: Developed and Validated in the Tohoku Medical Megabank Project.

    Naoko Mori, Shunji Mugikura, Atsushi Hozawa, Makiko Taira, Hiroaki Hashizume, Atsushi Sekiguchi, Mitsunari Abe, Michiyo Kasai, Tomo Saito, Kengo Kinoshita, Nobuo Fuse, Shinichi Kuriyama, Masayuki Yamamoto

    The Tohoku journal of experimental medicine　2025/01/16

    DOI： 10.1620/tjem.2025.J006 　

  26. Degree of housing damage caused by the Great East Japan Earthquake and all-cause mortality in the community-based cohort study of the Tohoku Medical Megabank Project. International-journal

    Naoki Nakaya, Kumi Nakaya, Mana Kogure, Yuka Kotozaki, Rieko Hatanaka, Ippei Chiba, Sayuri Tokioka, Masato Takase, Satoshi Nagaie, Hideki Ohmomo, Takahito Nasu, Nobuo Fuse, Kozo Tanno, Atsushi Hozawa

    Journal of epidemiology and community health　2025/01/15

    DOI： 10.1136/jech-2024-223084 　

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    BACKGROUND: Natural disasters may have negative health effects on survivors. However, long-term observations on this are lacking. Therefore, this study investigated the association between the degree of housing damage caused by the Great East Japan Earthquake (GEJE) and all-cause mortality using the data from the cohort study conducted by the Tohoku Medical Megabank (TMM) Project in disaster-stricken areas. METHODS: The community-based cohort study of the TMM Project which conducted a baseline survey from May 2013 to March 2016 collected data using questionnaires and blood and urine tests. The present large-scale prospective cohort study was a follow-up survey in which the degree of house damage and all-cause mortality were analysed using Cox proportional hazards regression, adjusting for sex, age and other potentially confounding variables. The degree of house damage was categorised into 'did not live in the disaster area', 'no damage', 'small-scale damage' and 'large-scale damage'. Among the 58 320 participants, 1763 deaths were confirmed during the follow-up which averaged 6.5 years. RESULTS: The multivariate analysis showed a hazard ratio (95% CI) of 0.96 (0.82 to 1.13) for those who did not live in the disaster area, 0.98 (0.87 to 1.10) for small-scale damage and 0.98 (0.85 to 1.14) for large-scale damage, compared with no damage, but no significant association with all-cause mortality was observed. CONCLUSION: The results of this large-scale prospective cohort study of GEJE survivors showed no significant relationship between the degree of house damage and all-cause mortality. Further long-term follow-up studies are needed to examine the long-term health effects of natural disasters on survivors.

  27. Has the impact of cigarette smoking on mortality been underestimated by overlooking second-hand smoke? Tohoku medical megabank community-based cohort study. International-journal

    Masato Takase, Naoki Nakaya, Kozo Tanno, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Kotaro Nochioka, Takahiro Tabuchi, Taku Obara, Mami Ishikuro, Yuka Kotozaki, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Takahito Nasu, Hideki Ohmomo, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Yoko Izumi, Atsushi Hozawa

    BMJ public health　3　(1)　e001746　2025

    DOI： 10.1136/bmjph-2024-001746 　

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    OBJECTIVES: Previous studies have assessed the impact of active smoking on mortality using the population-attributable fraction (PAF). However, these studies have not included second-hand smoking (SHS), potentially underestimating smoking's impact. We compared the PAF from active smoking alone with the PAF, including SHS exposure. DESIGN: Prospective cohort study. SETTING: A community-based cohort study in Japan. PARTICIPANTS: 40 796 participants aged ≥20 years. MAIN OUTCOME MEASURES: SHS was defined as inhaling someone else's cigarette smoke at the workplace or home in the past year. We classified smoking status and SHS into ten categories: never-smoker without SHS, never-smoker with SHS, past smoker without SHS, past smoker with SHS, current smoker 1-9 cigarettes/day without SHS, current smoker 1-9 cigarettes/day with SHS, 10-19 cigarettes/day without SHS, 10-19 cigarettes/day with SHS, ≥20 cigarettes/day without SHS and ≥20 cigarettes/day with SHS. The main outcome was all-cause mortality. RESULTS: During the median follow-up period of 6.5 (5.7-7.5) years, 788 men and 328 women died. For men, compared with never-smokers without SHS, past smokers without SHS (HR, 1.39 [95% CI, 1.11 to 1.73]) and past smokers with SHS (HR, 1.48 (95% CI, 1.10 to 2.00)) were associated with all-cause mortality. For women, never-smokers with SHS had a significantly higher risk of all-cause mortality (HR, 1.36 (95% CI, 1.00 to 1.84)). Without considering SHS, 28.0% and 2.3% of all-cause mortality in men and women, respectively, were attributable to past and current smoking. Including SHS, PAF increased to 31.3% in men and 8.4% in women. CONCLUSIONS: We clarified that smoking's impact was underestimated by not accounting for SHS, especially in women. Information on SHS is crucial for understanding smoking's health impact. This study supports the importance of avoiding smoking and preventing SHS.

  28. Respiratory syncytial virus infection, non-respiratory syncytial virus respiratory infections, and later wheezing. International-journal

    Ippei Takahashi, Genki Shinoda, Fumihiko Ueno, Fumiko Matsuzaki, Aoi Noda, Keiko Murakami, Mami Ishikuro, Taku Obara, Yoshikazu Nakayama, Atsushi Momose, Naho Tsuchiya, Satoshi Nagaie, Soichi Ogishima, Gen Tamiya, Nobuo Fuse, Atsushi Hozawa, Junichi Sugawara, Shigeo Kure, Shinichi Kuriyama

    Pediatrics international : official journal of the Japan Pediatric Society　67　(1)　e70050　2025

    DOI： 10.1111/ped.70050 　

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    BACKGROUND: Studies investigating whether respiratory syncytial virus (RSV) infection, non-RSV respiratory infections, respiratory-related disorders, and non-respiratory-related disorders are associated with subsequent wheezing are limited in Japan. We aimed to elucidate the relationship between hospitalization for RSV infection, non-RSV respiratory infections, respiratory-related disorders, as well as non-respiratory-related disorders and subsequence wheezing in Japanese children. METHODS: This study included 7340 children and was conducted under the TMM BirThree Cohort Study (Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study). Data was collected from birth records and questionnaires. We categorized hospitalization history into five categories: "no hospitalization," hospitalizations for "RSV infection," "non-RSV respiratory infections," "respiratory-related disorders," and "non-respiratory-related disorders." The association of the five categories with later wheezing at 3 years of age was evaluated using multivariable logistic regression analysis. RESULTS: After adjusting for covariates, an association was shown between hospitalization under 2 years of age and later wheezing (odds ratio [OR] = 2.78; 95% confidence interval [CI] = 1.97-3.88 for "RSV infection"; OR = 2.61; 95% CI = 1.44-4.57 for "non-RSV respiratory infections"; and OR = 3.33; 95% CI = 2.43-4.54 for "respiratory-related disorders"). CONCLUSION: Hospitalization of children under 2 years of age for RSV infection as well as non-RSV respiratory infections and respiratory-related disorders were associated with subsequent wheezing.

  29. Genome-Wide Association Study of Intraocular Pressure in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study. International-journal

    Nobuo Fuse, Hayato Anzawa, Miyuki Sakurai, Ikuko N Motoike, Satoshi Nagaie, Tomohiro Nakamura, Akiko Miyazawa, Eiichi N Kodama, Masatsugu Orui, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Makiko Taira, Ritsuko Shimizu, Naoki Nakaya, Mami Ishikuro, Taku Obara, Fuji Nagami, Soichi Ogishima, Fumiki Katsuoka, Kazuki Kumada, Shinichi Kuriyama, Atsushi Hozawa, Yoko Izumi, Kengo Kinoshita, Masayuki Yamamoto

    Ophthalmology science　5　(5)　100821-100821　2025

    DOI： 10.1016/j.xops.2025.100821 　

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    PURPOSE: This study was conducted to elucidate the distribution and determinants of ocular biometric parameters and to assess the association between intraocular pressure (IOP) and single nucleotide polymorphisms (SNPs) in the Japanese population-based genome cohort studies. DESIGN: Cross-sectional analysis involving genome-wide association studies (GWASs). PARTICIPANTS: In total, 22 150 participants aged >18 years from the population cohort (Community-Based Cohort [CommCohort]) and 11 302 participants from the Birth and Three-Generation (BirThree) Cohort of the Tohoku Medical Megabank Organization Eye Study were examined. METHODS: Participant underwent interviews, ophthalmic and physiological examinations, laboratory tests, and microarray analyses. Genome-wide association studies were conducted in the CommCohort (discovery stage) and the BirThree Cohort (replication stage), followed by a meta-analysis. Associations of SNPs and IOP were evaluated using a genome-wide significance threshold (5 × 10- 8). MAIN OUTCOME MEASURES: Association of SNPs with IOP and distributions of IOP by sex and age. RESULTS: In the discovery stage, the mean IOP of the right and left eye was 13.95 and 14.02 mmHg, respectively. In the replication stage, the corresponding values were 14.32 and 14.27 mmHg, respectively. A significant age-related reduction in IOP was observed in both stages (P < 0.001). Genome-wide association studies identified 573 and 2 genome-wide significant SNPs in the discovery and replication stages, respectively. Meta-analysis revealed 1601 significant SNPs across 21 loci on 11 chromosomes (Chrs). Of these loci, 17 were previously known to be associated with IOP or glaucoma, while four-septin-8 (SEPT8; Chr5), aldehyde dehydrogenase 2 (ALDH2; Chr12), collagen type VI alpha 2 chain (COL6A2; Chr21), and Wnt family member 7B (WNT7B; Chr22)-were newly identified. CONCLUSIONS: This large-scale GWAS in a Japanese population identified 21 loci associated with IOP, including 4 novel loci. The findings highlight both genetic similarities and population-specific variations in SNPs influencing IOP and provide valuable insights to enhance eye health care, including glaucoma management. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  30. Prevalence and Associations of Epiretinal Membrane by OCT in a Japanese Population-Based Cohort: Tohoku Medical Megabank Organization Eye Study. International-journal

    Akihiko Shiraki, Atsushi Hirayama, Nobuo Fuse, Ryo Kawasaki, Satoko Fujimoto, Tomoyuki Okazaki, Susumu Sakimoto, Takatoshi Maeno, Makiko Taira, Tomo Saito, Tomohiro Nakamura, Soichi Ogishima, Atsushi Hozawa, Kengo Kinoshita, Masayuki Yamamoto, Kohji Nishida

    Ophthalmology science　5　(4)　100752-100752　2025

    DOI： 10.1016/j.xops.2025.100752 　

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    PURPOSE: To examine the prevalence of epiretinal membrane (ERM) according to the OCT-based severity scales, and to describe associations focusing on the impact of smoking and axial length of the globe. DESIGN: Cross-sectional study. PARTICIPANTS: The baseline examination cohort comprised participants from the Tohoku Medical Megabank community cohort recruited from 2013 to 2017. METHODS: In total, 38 118 eyes of 19 486 participants were classified with ERM staging. The characteristics of ERM severity were analyzed, and the association between the prevalence of ERM and ocular and systemic parameters was investigated using logistic regression models. Cubic spline models were constructed to visualize the relationships with lifetime smoking exposure and axial lengths. Regarding ERM severity, the associations between stage 1 and stage 2 or more were analyzed with multivariate analysis. MAIN OUTCOME MEASURES: Epiretinal membrane prevalence at each stage determined via OCT and factors associated with ERM presence and severity. RESULTS: The prevalence of ERM was 2.3% per eye (3.6% per person), with a predominance at stage 1. The presence of severe ERM stages was higher in older individuals. The multivariate logistic analysis revealed that older age, female sex, and long axial length were associated with a higher prevalence of ERM. In a multivariate analysis stratified by sex, glaucoma was also identified as a significant factor associated with the prevalence of ERM in women. In the cubic spline model, no consistent trend was observed between smoking and ERM prevalence. However, a U-shaped relationship was indicated between axial length and ERM prevalence. Epiretinal membrane severity highlighted older age, alcohol consumption, and very long axial length as significantly associated compared with stage 1. CONCLUSIONS: Epiretinal membrane prevalence was significantly associated with older age, female sex, and long axial length. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  31. Age-disproportionate atrophy in Alzheimer's disease and Parkinson's disease spectra. International-journal

    Kenji Yoshinaga, Toma Matsushima, Mitsunari Abe, Tsunehiko Takamura, Hiroki Togo, Noritaka Wakasugi, Nobukatsu Sawamoto, Toshiya Murai, Toshiki Mizuno, Teruyuki Matsuoka, Kazuaki Kanai, Hiroshi Hoshino, Atsushi Sekiguchi, Nobuo Fuse, Shunji Mugikura, Takashi Hanakawa

    Alzheimer's & dementia (Amsterdam, Netherlands)　17　(1)　e70048　2025

    DOI： 10.1002/dad2.70048 　

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    INTRODUCTION: Brain age gap (BAG), defined as the difference between MRI-predicted 'brain age' and chronological age, can capture information underlying various neurological disorders. We investigated the pathophysiological significance of the BAG across neurodegenerative disorders. METHODS: We developed a brain age estimator using structural MRIs of healthy-aged individuals from one cohort study. Subsequently, we applied this estimator to people with Alzheimer's disease spectra (AD) and Parkinson's disease (PD) from another cohort study. We investigated brain sources responsible for BAGs among these groups. RESULTS: Both AD and PD exhibited a positive BAG. Brain sources showed overlapping, yet partially segregated, neuromorphological differences between these groups. Furthermore, employing with t-distributed stochastic neighbor embedding on the brain sources, we subclassified PD into two groups with and without cognitive impairment. DISCUSSION: Our findings suggest that brain age estimation becomes a clinically relevant method for finely stratifying neurodegenerative disorders. HIGHLIGHTS: Brain age estimated from structure MRI data was greater than chronological age in patients with Alzheimer's disease/mild cognitive impairment or Parkinson's disease.Brain regions attributed to brain age estimation were located mainly in the fronto-temporo-parietal cortices but not in the motor cortex or subcortical regions.Brain sources responsible for the brain age gaps revealed roughly overlapping, yet partially segregated, neuromorphological differences between participants with Alzheimer's disease/mild cognitive impairment and Parkinson's disease.Participants with Parkinson's disease were subclassified into two groups (with and without cognitive impairment) based on brain sources responsible for the brain age gaps.

  32. Basic Science and Pathogenesis. International-journal

    Makiko Taira, Nobuo Fuse, Andrew J Saykin, Fuji Nagami, Kengo Kinoshita, Masayuki Yamamoto

    Alzheimer's & dementia : the journal of the Alzheimer's Association　20 Suppl 1　e093405　2024/12

    DOI： 10.1002/alz.093405 　

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    BACKGROUND: Dementia is age-related with a significant genetic contribution, yet genome-wide association studies have not fully accounted for heritability. This discrepancy may in part be due to reliance on SNPs and small indels. Whole-genome sequencing (WGS) data in the Japanese population may reveal population-specific susceptibility loci for dementia. Retinal imaging with optical coherence tomography (OCT) is noninvasive, reproducible, and can detect thinning associated with progressive neurodegeneration. Association of population-specific genetic susceptibility loci with retinal thinning and cognitive decline may reveal novel aspects of dementia risk and pathophysiology. METHOD: Among participants with WGS data from the Tohoku Medical Megabank Organization (ToMMo) Ophthalmology Study ("ToMMo Eye Study"), individuals with adequate quality data on retinal nerve fiber layer and ganglion cell layer thickness from spectral-domain optical coherence tomography (SD-OCT) scans were selected. Since retinal thinning also occurs in glaucoma, we performed a GWAS using age, sex, and 10 principal components as covariates using SAGE1.2 to obtain a set of genes responsible for glaucoma and confirm that the genotyping was successful. We then attempted to identify susceptibility loci for cognitive decline by using (1) the Mini-Mental State Examination, Japanese version (MMSE-J), (2) the Montreal Cognitive Assessment, Japanese version (MoCA-J), and (3) the Mini-COG© (a simple screening for early detection of dementia, Japanese version) scores as associated factors, respectively. Furthermore, these validation results were also compared with those obtained from GWAS using imputation data performed on custom arrays (Japonica ArrayTM, v2 or NEO) for Japanese. RESULT: 84 significant (p < 5.0E-8) genome-wide susceptibility loci (hg38) of RNFL were detected on 14K WGS-based study (the top hit locus: Chr14, SIX6 gene, P = 4.50E-46). There were many genetic loci that have already been reported to be associated with glaucoma susceptibility, including the above locus. Among the results of GWAS for cognitive decline combining the three cognitive scores after normalization to z-scores, several loci have shown significant susceptibility in both of RNFL and cognitive rating scale. Some loci suggested more than a high or moderate effect of altering protein efficacy. CONCLUSION: We present an initial WGS-based genetic study of retinal thickness and cognitive decline in the Japanese population.

  33. Identification of risk loci for postpartum depression in a genome-wide association study. International-journal

    Xue Li, Nagahide Takahashi, Akira Narita, Yukako Nakamura, Mika Sakurai-Yageta, Keiko Murakami, Mami Ishikuro, Taku Obara, Masahiro Kikuya, Fumihiko Ueno, Hirohito Metoki, Hisashi Ohseto, Ippei Takahashi, Tomohiro Nakamura, Noriko Warita, Tomoka Shoji, Zhiqian Yu, Chiaki Ono, Natsuko Kobayashi, Saya Kikuchi, Tasuku Matsuki, Fuji Nagami, Soichi Ogishima, Junichi Sugawara, Tetsuro Hoshiai, Masatoshi Saito, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Yaegashi, Norio Ozaki, Gen Tamiya, Shinichi Kuriyama, Hiroaki Tomita

    Psychiatry and clinical neurosciences　78　(11)　712-720　2024/11

    DOI： 10.1111/pcn.13731 　

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    AIM: Genome-wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD-associated loci. METHODS: The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders. RESULTS: A meta-analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10-8) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over-represented in categories including long-term depression, GnRH signaling, glutamatergic synapse, oxytocin signaling, and Rap1 signaling. CONCLUSION: The current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis.

  34. Associations between leisure time, non-leisure time physical activity, and kidney function in Japanese adults: a cross-sectional study. International-journal

    Ippei Chiba, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Sayuri Tokioka, Tomohiro Nakamura, Satoshi Nagaie, Soichi Ogishima, Taku Obara, Toshimi Sato, Nobuo Fuse, Yoko Izumi, Shinichi Kuriyama, Atsushi Hozawa

    BMC nephrology　25　(1)　354-354　2024/10/16

    DOI： 10.1186/s12882-024-03813-6 　

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    BACKGROUND: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. METHODS: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. RESULTS: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables. CONCLUSIONS: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function.

  35. Genetic Risk, Lifestyle Adherence, and Risk of Developing Hyperuricaemia in a Japanese Population

    Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Akira Narita, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Biobank Japan Project; Koichi Matsuda, Yoko Izumi, Kengo Kinoshita, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

    Rheumatology　2024/09/13

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/rheumatology/keae492 　

    ISSN： 1462-0324

    eISSN： 1462-0332

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    Abstract Objective To investigate the inter-relationships among genetic risk, healthy lifestyle adherence, and hyperuricaemia susceptibility. Methods This prospective cohort study was conducted with 7,241 hyperuricaemia-free individuals aged ≥ 20 years from the Tohoku Medical Megabank Community-based cohort study. A comprehensive lifestyle score included body mass index, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and hyperuricaemia incidence and calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dl or a self-reported history of hyperuricaemia. Results Of the 7,241 adults (80.7% females; mean [SD] age: 57.7 [12.6] years), 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up. Genetic risk correlated with hyperuricaemia development (P for interaction = 0.287), and lifestyle risks were independently associated. Those with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% confidence interval [CI]: 2.61–12.10). Although not statistically significant, incorporating the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736–0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751–0.819 for lifestyle and PRS; p = 0.07). Conclusion : A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.

  36. Association of olfactory and cognitive function test scores with hippocampal and amygdalar grey matter volume: a cross-sectional study

    Shuichi Sato, Takao Imaeda, Shunji Mugikura, Naoko Mori, Masaki Takanashi, Kazumi Hayakawa, Tomo Saito, Makiko Taira, Akira Narita, Mana Kogure, Ippei Chiba, Rieko Hatanaka, Kumi Nakaya, Ikumi Kanno, Ryosuke Ishiwata, Tomohiro Nakamura, Ikuko N. Motoike, Naoki Nakaya, Seizo Koshiba, Kengo Kinoshita, Shinichi Kuriyama, Soichi Ogishima, Fuji Nagami, Nobuo Fuse, Atsushi Hozawa

    Scientific Reports　14　(1)　2024/08/19

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-024-69726-4 　

    eISSN： 2045-2322

  37. Mutations of CYP1B1 and FOXC1 genes for childhood glaucoma in Japanese individuals.

    Nobuo Fuse, Masae Kimura, Ai Shimizu, Seizo Koshiba, Teruhiko Hamanaka, Makoto Nakamura, Nobuo Ishida, Hiroshi Sakai, Yoko Ikeda, Kazuhiko Mori, Atsushi Endo, Masao Nagasaki, Fumiki Katsuoka, Jun Yasuda, Yoichi Matsubara, Toru Nakazawa, Masayuki Yamamoto

    Japanese journal of ophthalmology　2024/08/19

    DOI： 10.1007/s10384-024-01103-0 　

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    PURPOSE: To explore the frequency and positions of genetic mutations in CYP1B1 and FOXC1 in a Japanese population. STUDY DESIGN: Molecular genetic analysis. METHODS: Genomic DNA was extracted from 31 Japanese patients with childhood glaucoma (CG) from 29 families. We examined the CYP1B, FOXC1, and MYOC genes using Sanger sequencing and whole-exome sequencing (WES). RESULTS: For CYP1B1, we identified 9 families that harbored novel mutations, p.A202T, p.D274E, p.Q340*, and p.V420G; the remaining mutations had been previously reported. When mapped to the CYP1B1 protein structure, all mutations appeared to influence the enzymatic activity of CYP1B1 by provoking structural deformity. Five patients were homozygotes or compound heterozygotes, supporting the recessive inheritance of the CYP1B1 mutations in CG. In contrast, four patients were heterozygous for the CYP1B1 mutation, suggesting the presence of regulatory region mutations or strong modifiers. For the FOXC1 gene, we identified 3 novel mutations, p.Q23fs, p.Q70R, and p.E163*, all of which were identified in a heterozygous state. No mutation was found in the MYOC gene in these CG patients. All individuals with CYP1B1 and FOXC1 mutations were severely affected by early-onset CG. In the CYP1B1-, FOXC1-, and MYOC-negative families, we also searched for variants in the other candidate genes reported for CG through WES, but could not find any mutations in these genes. CONCLUSIONS: Our analyses of 29 CG families revealed 9 families with point mutations in the CYP1B1 gene, and four of those patients appeared to be heterozygotes, suggesting the presence of complex pathogenic mechanisms. FOXC1 appears to be another major causal gene of CG, indicating that panel sequencing of CYP1B1 and FOXC1 will be useful for diagnosis of CG in Japanese individuals.

  38. The association of birth weight and current BMI on the risk of hypertension: the Tohoku medical megabank community-based cohort study. International-journal

    Hiromi Himuro, Mana Kogure, Naoki Nakaya, Tomohiro Nakamura, Rieko Hatanaka, Ippei Chiba, Kumi Nakaya, Naho Tsuchiya, Takumi Hirata, Masatsugu Orui, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Akira Uruno, Nobuo Fuse, Satoshi Nagaie, Soichi Ogishima, Mami Ishikuro, Taku Obara, Yoko Izumi, Masatoshi Saito, Shinichi Kuriyama, Atsushi Hozawa, Junichi Sugawara

    Hypertension research : official journal of the Japanese Society of Hypertension　2024/08/08

    DOI： 10.1038/s41440-024-01827-z 　

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    This study aimed to investigate the association of combination of birth weight and current body mass index (BMI) with the risk of hypertension in adulthood. This cross-sectional study used data from the Tohoku Medical Megabank Community-based Cohort Study conducted in Japan. A total of 10,688 subjects aged ≥20 years were eligible. We calculated the least square (LS) means of systolic blood pressure (SBP) and trend tests were performed to evaluate the linear relationships between birth weight categories and SBP. We also used a multivariate logistic regression analysis to assess the risk of hypertension associated with the combination of birth weight and current BMI. There was a statistically inverse association between birth weight and SBP in the 20-64 age group, but no significant association in the ≥65 age group. Low birth weight (LBW) with normal BMI group had a higher risk of hypertension than the normal or high birth weight groups with normal BMI. Furthermore, the group with LBW and BMI ≥25.0 kg/m2 was the highest risk for hypertension (adjusted odds ratio: 2.73; 95% CI, 2.04-3.65) compared to the reference group (birth weight 2500-3499 g and BMI 18.5-24.9 kg/m2). There was a significant association between LBW and subsequent risk of hypertension. In addition, participants with lower birth weights had a higher risk of hypertension than those with higher birth weights. However, even in participants with a lower birth weight, the risk of hypertension could be reduced when they maintained an optimal BMI.

  39. Fractional exhaled nitric oxide distribution and its relevant factors in the general adult population and its healthy subpopulation. International-journal

    Mitsuhiro Yamada, Masato Takase, Kumi Nakaya, Tomohiro Nakamura, Mana Kogure, Naoki Nakaya, Naoya Fujino, Tsutomu Tamada, Chikashi Iwasaki, Manami Suzuki, Shuichiro Matsumoto, Nobuo Fuse, Akira Uruno, Kazuki Kumada, Soichi Ogishima, Shinichi Kuriyama, Masakazu Ichinose, Hisatoshi Sugiura, Atsushi Hozawa

    The journal of allergy and clinical immunology. Global　3　(3)　100253-100253　2024/08

    DOI： 10.1016/j.jacig.2024.100253 　

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    BACKGROUND: Measurement of fractional exhaled nitric oxide (Feno) has been used in the diagnosis and management of asthma. Understanding the distribution of Feno in a larger resident population and its "healthy" subpopulation would contribute to the interpretation of Feno in clinical practice. OBJECTIVE: This study aimed to investigate the distribution and its associated factors in the adult population and its healthy subpopulations. METHODS: We conducted a cross-sectional study of 8,638 men and 17,288 women aged 20 years or older living in Miyagi prefecture, Japan. We investigated the distribution of Feno and its associated factors in all subjects, a subpopulation with no history of upper and lower airway diseases (healthy subpopulation 1), and a subpopulation with no history of upper and lower airway diseases, normal lung function, and no positivity for other biomarkers of type 2 inflammation (healthy subpopulation 2). RESULTS: The distribution of Feno in healthy subpopulations, especially in healthy subpopulation 2 (median [interquartile range], 17 [12-23] with 95th percentile of 36 ppb) was lower than in all subjects (19 [13-26] ppb with 95th percentile of 47 ppb). In healthy subpopulation 1, 10.3% had elevated Feno (≥35 ppb), and elevated Feno was positively associated with factors including obstructive ventilatory defect, blood eosinophilia, house dust mite-specific IgE positivity, and history of hypertension. Male sex was associated with elevated Feno in all subjects and healthy subpopulations. CONCLUSION: The distribution of Feno in the healthy subpopulation supports the validity of the criteria (≥35 ppb) currently used in Japan for the diagnosis of asthma.

  40. Urgent Notification Intervention of Home Blood Pressure in Cohort Studies of the Tohoku Medical Megabank Project.

    Eiichi N Kodama, Makiko Taira, Hideyasu Kiyomoto, Tomohiro Nakamura, Satoshi Nagaie, Shinichi Kuriyama, Atsushi Hozawa, Junichi Sugawara, Fuji Nagami, Akira Uruno, Jun Nakaya, Hirohito Metoki, Masaki Sakaida, Masahiro Kikuya, Yoichi Suzuki, Kiyoshi Ito, Yohei Hamanaka, Kichiya Suzuki, Shigeo Kure, Nobuo Yaegashi, Nobuo Fuse, Ritsuko Shimizu, Masayuki Yamamoto

    JMA journal　7　(3)　342-352　2024/07/16

    DOI： 10.31662/jmaj.2023-0215 　

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    INTRODUCTION: The Tohoku Medical Megabank (TMM) was established for creative reconstruction from the Great East Japan Earthquake and tsunami in 2011. Two prospective genome cohort studies in Miyagi prefecture have successfully recruited approximately 127,000 participants. The health status of these individuals was evaluated at the initial recruitment, and follow-up health checkups have been conducted every 5 years. During these health checkups, unexpected critical values were encountered, which prompted us to develop an urgent notification system. METHODS: We analyzed the frequency of critical values observed in home blood pressure (HBP) test in an urgent notification office (UNO). We returned the critical values by urgent notification before the notifications of regular results. In addition, the impact of the TMM urgent notification on the participants was evaluated. RESULTS: We issued urgent notifications of the critical values of extremely high HBP. Of the 21,061 participants who underwent HBP measurements, 256 (1.2%) met the criteria for urgent notification. It was found that abnormalities in blood sugar levels, renal function, and lipid values were frequently concurrent with the abnormal HBP readings. Annual questionnaires administered after the urgent notification, approximately 60% of those went to hospitals or clinics. CONCLUSIONS: The urgent notification system for hypertensive emergency with HBP in the TMM was well accepted by the participants and encouraged them to seek medical care. The system has been useful in addressing the prolonged healthcare problems and in promoting health care in large-scale disaster damaged areas.

  41. Depressive symptoms as risk factors for the onset of home hypertension: a prospective cohort study. International-journal

    Sayuri Tokioka, Naoki Nakaya, Rieko Hatanaka, Kumi Nakaya, Mana Kogure, Ippei Chiba, Kotaro Nochioka, Hirohito Metoki, Takahisa Murakami, Michihiro Satoh, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Satoshi Nagaie, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

    Hypertension research : official journal of the Japanese Society of Hypertension　2024/07/10

    DOI： 10.1038/s41440-024-01790-9 　

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    Depression is comorbid with somatic diseases; however, the relationship between depressive symptoms and hypertension (HT), a risk factor for cardiovascular events, remains unclear. Home blood pressure (BP) is more reproducible and accurately predictive of cardiovascular diseases than office BP. Therefore, we focused on home BP and investigated whether depressive symptoms contributed to the future onset of home HT. This prospective cohort study used data from the Tohoku Medical Megabank Community-Cohort Study (conducted in the Miyagi Prefecture, Japan) and included participants with home normotension (systolic blood pressure (SBP) < 135 mmHg and diastolic blood pressure (DBP) < 85 mmHg). Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale-Japanese version at the baseline survey. In the secondary survey, approximately 4 years later, the onset of home HT was evaluated (SBP ≥ 135 mmHg or DBP ≥ 85 mmHg) and was compared in participants with and without depressive symptoms. Of the 3 082 (mean age: 54.2 years; females: 80.9%) participants, 729 (23.7%) had depressive symptoms at the baseline survey. During the 3.5-year follow-up, 124 (17.0%) and 388 (16.5%) participants with and without depressive symptoms, respectively, developed home HT. Multivariable adjusted odds ratios were 1.37 (95% confidence interval (CI): 1.02-1.84), 1.18 (95% CI: 0.86-1.61), and 1.66 (95% CI: 1.17-2.36) for home, morning, and evening HT, respectively. This relationship was consistent in the subgroup analyses according to age, sex, BP pattern, and drinking habit. Depressive symptoms increased the risk of new-onset home HT, particularly evening HT, among individuals with home normotension. This prospective cohort study revealed that depressive symptoms are risk factors for new-onset home hypertension, particularly evening hypertension among individuals with home normotension. Assessing home blood pressure in individuals with depressive symptoms is important for the prevention of hypertension and concomitant cardiovascular diseases.

  42. Associations of combined genetic and lifestyle risks with hypertension and home hypertension. International-journal

    Masato Takase, Takumi Hirata, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Akira Narita, Hirohito Metoki, Michihiro Satoh, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

    Hypertension research : official journal of the Japanese Society of Hypertension　2024/06/24

    DOI： 10.1038/s41440-024-01705-8 　

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    No study, to our knowledge, has constructed a polygenic risk score based on clinical blood pressure and investigated the association of genetic and lifestyle risks with home hypertension. We examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. In a cross-sectional study of 7027 Japanese individuals aged ≥20 years, we developed a lifestyle score based on body mass index, alcohol consumption, physical activity, and sodium-to-potassium ratio, categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score was constructed with the target data (n = 1405) using publicly available genome-wide association study summary statistics from BioBank Japan. Using the test data (n = 5622), we evaluated polygenic risk score performance and examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. Hypertension and home hypertension were defined as blood pressure measured at a community-support center ≥140/90 mmHg or at home ≥135/85 mmHg, respectively, or self-reported treatment for hypertension. In the test data, 2294 and 2322 participants had hypertension and home hypertension, respectively. Both polygenic risk and lifestyle scores were independently associated with hypertension and home hypertension. Compared with those of participants with low genetic risk and an ideal lifestyle, the odds ratios for hypertension and home hypertension in the low genetic risk and poor lifestyle group were 1.94 (95% confidence interval, 1.34-2.80) and 2.15 (1.60-2.90), respectively. In summary, lifestyle is important to prevent hypertension; nevertheless, participants with high genetic risk should carefully monitor their blood pressure despite a healthy lifestyle.

  43. Genetic Risk, Healthy Lifestyle Adherence, and Risk of Developing Diabetes in the Japanese Population.

    Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Akira Narita, Taku Obara, Mami Ishikuro, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Koichi Matsuda, Yoko Izumi, Kengo Kinoshita, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

    Journal of atherosclerosis and thrombosis　2024/06/22

    DOI： 10.5551/jat.64906 　

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    AIM: This study examined the relationship between genetic risk, healthy lifestyle, and risk of developing diabetes. METHODS: This prospective cohort study included 11,014 diabetes-free individuals ≥ 20 years old from the Tohoku Medical Megabank Community-based cohort study. Lifestyle scores, including the body mass index, smoking, physical activity, and gamma-glutamyl transferase (marker of alcohol consumption), were assigned, and participants were categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score (PRS) was constructed based on the type 2 diabetes loci from the BioBank Japan study. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and diabetes incidence and to calculate the area under the receiver operating characteristic curve (AUROC). RESULT: Of the 11,014 adults included (67.8% women; mean age [standard deviation], 59.1 [11.3] years old), 297 (2.7%) developed diabetes during a mean 4.3 (0.8) years of follow-up. Genetic and lifestyle score is independently associated with the development of diabetes. Compared with the low genetic risk and ideal lifestyle groups, the odds ratio was 3.31 for the low genetic risk and poor lifestyle group. When the PRS was integrated into a model including the lifestyle and family history, the AUROC significantly improved to 0.719 (95% confidence interval [95% CI]: 0.692-0.747) compared to a model including only the lifestyle and family history (0.703 [95% CI, 0.674-0.732]). CONCLUSION: Our findings indicate that adherence to a healthy lifestyle is important for preventing diabetes, regardless of genetic risk. In addition, genetic risk might provide information beyond lifestyle and family history to stratify individuals at high risk of developing diabetes.

  44. Relationship between traditional risk factors for hypertension and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study. International-journal

    Masato Takase, Naoki Nakaya, Kozo Tanno, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Tomohiro Nakamura, Takumi Hirata, Taku Obara, Mami Ishikuro, Yuka Kotozaki, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Hideki Ohmomo, Nobuo Fuse, Junichi Sugawara, Atsushi Shimizu, Yoko Izumi, Shinichi Kuriyama, Atsushi Hozawa

    Hypertension research : official journal of the Japanese Society of Hypertension　47　(6)　1533-1545　2024/06

    DOI： 10.1038/s41440-024-01582-1 　

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    Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23-45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.

  45. Associations between housing and psychological damage by earthquake and modifiable risk factors for dementia in general older adults: Tohoku Medical Megabank community-based cohort study.

    Ippei Chiba, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Sayuri Tokioka, Tomohiro Nakamura, Satoshi Nagaie, Nobuo Fuse, Taku Obara, Yuka Kotozaki, Kozo Tanno, Shinichi Kuriyama, Atsushi Hozawa

    Geriatrics & gerontology international　2024/05/03

    DOI： 10.1111/ggi.14867 　

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    AIM: To evaluate the association between housing and psychological damage caused by the Great East Japan Earthquake (GEJE) and modifiable risk factors (MRFs) of dementia for general population of older adults. METHODS: This cross-sectional study enrolled 29 039 community-dwelling older adults (mean age 69.1 ± 2.9 years, 55.5% women). We evaluated disaster-related damage (by complete or not complete housing damage) and psychological damage (by post-traumatic stress reaction [PTSR]) after the GEJE using a self-report questionnaire. MRFs encompassed the presence of depression, social isolation, physical inactivity, smoking, and diabetes. We examined the association between disaster-related damage and MRFs using ordinary least squares and modified Poisson regression models adjusted for sociodemographic and health status variables. RESULTS: Complete housing damage and PTSR were identified in 2704 (10.0%) and 855 (3.2%) individuals, respectively. The number of MRFs was significantly larger for the individuals with complete housing damage (β = 0.23; 95% confidence interval [CI]: 0.19-0.27) and PTSR (β = 0.60; 95% CI: 0.53-0.67). Prevalence ratios (PRs) for depression and physical inactivity were higher in individuals with complete housing damage. The PRs for all domains of the MRFs were significantly higher in individuals with PTSR. CONCLUSIONS: Housing and psychological damage caused by the GEJE were associated with an increased risk factor of dementia. To attenuate the risk of dementia, especially among older victims who have experienced housing and psychological damage after a disaster, multidimensional support across various aspects of MRFs is required. Geriatr Gerontol Int 2024; ••: ••-••.

  46. Factors Associated With the Prevalence of Irritable Bowel Syndrome: The Miyagi Part of the Tohoku Medical Megabank Project Community-based Cohort Study. International-journal

    Kumi Nakaya, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Satoshi Nagaie, Tomohiro Nakamura, Motoyori Kanazawa, Soichi Ogishima, Nobuo Fuse, Shin Fukudo, Atsushi Hozawa

    Journal of neurogastroenterology and motility　30　(2)　208-219　2024/04/30

    DOI： 10.5056/jnm23090 　

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    BACKGROUND/AIMS: The objective of this research is to examine factors related to irritable bowel syndrome (IBS) prevalence in a large population-based study. METHODS: A cross-sectional study was conducted with participants in the Miyagi part of the Tohoku Medical Megabank Project Community-Based cohort study who completed the Rome II Modular Questionnaire. Multivariate odds ratios (ORs) for the presence of IBS and 95% confidence intervals (95% CIs) for the reference group were calculated for each factor. Additionally, a stratified analysis was performed by sex and age group (20-49 years, 50-64 years, and ≥ 65 years). RESULTS: Among 16 252 participants, 3025 (18.6%) had IBS, comprising 750 men (15.5%) and 2275 women (19.9%). Multivariate ORs for the presence of IBS decreased significantly with each year of age (OR, 0.98; 95% CI, 0.98-0.99). Moreover, compared with the reference group, ORs for the presence of IBS were significantly higher in individuals whose home was partially damaged by the Great East Japan Earthquake, those with < 16 years of education, those who spent less time walking, those with high perceived stress (1.77, 1.57-2.01), those with high psychological distress (1.58, 1.36-1.82), and those with high symptoms of depression (1.76, 1.60-1.94). In stratified analyses, a significant relationship was found between psychological factors and IBS prevalence in all sex and age groups. CONCLUSIONS: This large cross-sectional population-based cohort study identified several factors associated with IBS prevalence. Psychological factors were significantly associated with IBS prevalence across all age groups and sexes.

  47. The Health History of First-Degree Relatives’ Dyslipidemia Can Affect Preferences and Intentions following the Return of Genomic Results for Monogenic Familial Hypercholesterolemia Peer-reviewed

    Tomoharu Tokutomi, Akiko Yoshida, Akimune Fukushima, Kayono Yamamoto, Yasushi Ishigaki, HIROSHI KAWAME, Nobuo Fuse, Fuji Nagami, Yoichi Suzuki, Mika Sakurai-Yageta, Akira Uruno, Kichiya Suzuki, Kozo Tanno, Hideki Ohmomo, Atsushi Shimizu, Masayuki Yamamoto, Makoto Sasaki

    Genes　2024/03/21

    DOI： 10.3390/genes15030384 　

  48. Association of physiological factors with grip and leg extension strength: tohoku medical megabank community-based cohort study. International-journal

    Yoshiaki Noji, Rieko Hatanaka, Naoki Nakaya, Mana Kogure, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Tomohiro Nakamura, Naho Tsuchiya, Haruki Momma, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Ryoichi Nagatomi, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

    BMC public health　24　(1)　714-714　2024/03/05

    DOI： 10.1186/s12889-024-18244-z 　

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    BACKGROUND: Upper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults. METHODS: We conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors. RESULTS: Grip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively. CONCLUSIONS: Grip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent.

  49. 追跡調査によって得られた日本人における眼軸伸長の危険因子の検討

    西村 尭幸, 國方 彦志, 高田 菜生子, 石川 誠, 千葉 一平, 中谷 直樹, 寶澤 篤, 布施 昇男, 中澤 徹

    日本眼科学会雑誌　128　(臨増)　233-233　2024/03

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  50. The Association of Urinary Sodium-to-Potassium Ratio and Estimated Urinary Sodium Excretion with Atrial Fibrillation among Participants without Hypertension(タイトル和訳中)

    時岡 紗由理, 中谷 直樹, 畑中 里衣子, 中谷 久美, 千葉 一平, 小暮 真奈, 後岡 広太郎, 大類 真嗣, 宇留野 晃, 小林 朋子, 児玉 栄一, 濱中 洋平, 布施 昇男, 寳澤 篤

    日本循環器学会学術集会抄録集　88回　PJ005-4　2024/03

    Publisher: (一社)日本循環器学会

  51. Progress report of the Tohoku Medical Megabank Community-Based Cohort Study: Study profile of the repeated center-based survey during second period in Miyagi Prefecture.

    Atsushi Hozawa, Kumi Nakaya, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Junichi Sugawara, Eiichi Kodama, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Naho Tsuchiya, Takumi Hirata, Akira Narita, Akito Tsuboi, Toru Tamahara, Akihito Otsuki, Maki Goto, Makiko Taira, Ritsuko Shimizu, Kichiya Suzuki, Taku Obara, Masahiro Kikuya, Hirohito Metoki, Mami Ishikuro, Inaho Danjoh, Soichi Ogishima, Satoshi Nagaie, Naoko Minegishi, Masahiro Hiratsuka, Kazuki Kumada, Ichiko Nishijima, Takahiro Nobukuni, Yumi Yamaguchi-Kabata, Fuji Nagami, Shigeo Kure, Nobuo Fuse, Kengo Kinoshita, Yoko Izumi, Shinichi Kuriyama, Masayuki Yamamoto

    Journal of epidemiology　2024/02/24

    DOI： 10.2188/jea.JE20230241 　

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    BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

  52. Relationships of Fat Mass Index and Fat-Free Mass Index with Low-Density Lipoprotein Cholesterol Levels in the Tohoku Medical Megabank Community-Based Cohort Study.

    Masato Takase, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Taku Obara, Mami Ishikuro, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Yoko Izumi, Shinichi Kuriyama, Atsushi Hozawa

    Journal of atherosclerosis and thrombosis　2024/02/06

    DOI： 10.5551/jat.64535 　

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    AIMS: Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the f at mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. RESULTS: Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. CONCLUSIONS: Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

  53. Alcohol Flushingと悪性腫瘍有病の関連 TMM計画地域住民コホート調査(宮城)

    土谷 祐馬, 中谷 久美, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 千葉 一平, 菅野 郁美, 小原 拓, 石黒 真美, 大類 正嗣, 永家 聖, 中村 智洋, 荻島 創一, 布施 昇男, 泉 陽子, 栗山 進一, 亀井 尚, 寳澤 篤

    Journal of Epidemiology　34　(Suppl.)　154-154　2024/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  54. 尿中Na、K、Na/K比と胃がん罹患との関連 東北メディカル・メガバンク計画地域住民コホート調査

    小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 小原 拓, 永家 聖, 布施 昇男, 泉 陽子, 栗山 進一, 中谷 直樹, 寳澤 篤

    Journal of Epidemiology　34　(Suppl.)　100-100　2024/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  55. 尿中ナトリウム/カリウム比と心房細動の関連の検討

    時岡 紗由理, 中谷 直樹, 畑中 里衣子, 千葉 一平, 中谷 久美, 小暮 真奈, 大類 正嗣, 宇留野 晃, 小林 朋子, 児玉 栄一, 濱中 洋平, 布施 昇男, 寳澤 篤

    Journal of Epidemiology　34　(Suppl.)　122-122　2024/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  56. 未発症のBRCA1/2病的バリアント保持者に対するサーベイランスの課題

    濱中 洋平, 多田 寛, 原田 成美, 宮下 穣, 江幡 明子, 佐藤 未来, 柳垣 美歌, 本成 登貴和, 川目 裕, 鈴木 洋一, 長神 風二, 布施 昇男, 大根田 絹子, 山本 雅之, 石田 孝宣

    日本乳癌検診学会学術総会プログラム抄録集　33回　148-148　2023/11

    Publisher: (NPO)日本乳癌検診学会

  57. The association between depressive symptoms and masked hypertension in participants with normotension measured at research center. International-journal

    Sayuri Tokioka, Naoki Nakaya, Kumi Nakaya, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Hirohito Metoki, Takahisa Murakami, Michihiro Satoh, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Satoshi Nagaie, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

    Hypertension research : official journal of the Japanese Society of Hypertension　2023/10/31

    DOI： 10.1038/s41440-023-01484-8 　

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    Masked hypertension is a risk factor for cardiovascular diseases. However, masked hypertension is sometimes overlooked owing to the requirement for home blood pressure measurements for diagnosing. Mental status influences blood pressure. To reduce undiagnosed masked hypertension, this study assessed the association between depressive symptoms and masked hypertension. This cross-sectional study used data from the Tohoku Medical Megabank Project Community-Based Cohort Study (conducted in Miyagi Prefecture, Japan, from 2013) and included participants with normotension measured at the research center (systolic blood pressure<140 mmHg and diastolic blood pressure <90 mmHg). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (Japanese version). Masked hypertension was defined as normotension measured at the research center and home hypertension (home systolic blood pressure ≥135 mmHg or home diastolic blood pressure ≥85 mmHg). The study comprised 6705 participants (mean age: 55.7 ± 13.7 years). Of these participants, 1106 (22.1%) without depressive symptoms and 393 (23.2%) with depressive symptoms were categorized to have masked hypertension. Sex-specific and age-adjusted least mean squares for home blood pressure, not for research blood pressure were significantly higher in the group with depressive symptoms in both sex categories. The multivariate odds ratio for masked hypertension in the patients with depressive symptoms was 1.72 (95% confidence interval: 1.26-2.34) in male participants and 1.30 (95% confidence interval: 1.06-1.59) in female ones. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at the research center. Depressive symptoms may be one of the risk factors for masked hypertension. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at research center.

  58. Relationship between nailfold capillaroscopy parameters and the severity of diabetic retinopathy. International-journal

    Tatsu Okabe, Hiroshi Kunikata, Masayuki Yasuda, Shinjiro Kodama, Yuta Maeda, Joe Nakano, Dan Takeno, Nobuo Fuse, Toru Nakazawa

    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie　2023/10/24

    DOI： 10.1007/s00417-023-06220-z 　

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    PURPOSE: To determine whether non-invasive measurements of the nailfold capillaries (NCs) are associated with the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: Eighty-three eyes of 83 patients with type 2 diabetes were enrolled. Sixty-three age-matched non-diabetic subjects served as controls. Diabetic patients were classified by the severity of their DR: non-DR (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). We used nailfold capillaroscopy to measure NC parameters, including number, length, width, and turbidity. RESULTS: Four NC parameters in the diabetic patients were significantly lower than in the controls (all P < 0.001). There was a statistically significant decrease in the NC parameters along with the increasing severity of DR (number: P = 0.02; all others: P < 0.001). Logistic regression analysis revealed that combining the systemic characteristics of age, sex, systolic blood pressure, estimated glomerular filtration rate, hemoglobin A1c level, and history of hypertension and dyslipidemia could indicate the presence of DR and PDR (the area under the receiver operating characteristic curve [AUC] = 0.81, P = 0.006; AUC = 0.87, P = 0.001, respectively). Furthermore, the discriminative power of DR was significantly improved (P = 0.03) by adding NC length to the systemic findings (AUC = 0.89, P < 0.001). CONCLUSION: NC measurement is a simple and non-invasive way to assess the risk of DR and its severity.

  59. The risk of withdrawal from hypertension treatment in coastal areas after the Great East Japan Earthquake: the TMM CommCohort Study

    Rieko Hatanaka, Naoki Nakaya, Mana Kogure, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Hideaki Hashimoto, Tomohiro Nakamura, Kotaro Nochioka, Taku Obara, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Akira Uruno, Eiichi N. Kodama, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

    Hypertension Research　2023/10/13

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41440-023-01454-0 　

    ISSN： 0916-9636

    eISSN： 1348-4214

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    Abstract This study aimed to examine whether risk of withdrawal from HTTx was higher in coastal areas that were severely damaged by tsunami than in inland areas. We conducted a cross-sectional study of 9218 participants aged ≥20 years in Miyagi, Japan. The odds ratios (ORs) and confidence interval (CI) for withdrawal from HTTx in coastal and inland groups were compared using multivariate logistic regression analysis, adjusting for potential confounders. In total, 194 of 5860 and 146 of 3358 participants in the inland and coastal groups, respectively, withdrew from HTTx treatment. OR (95%CI) of withdrawal from HTTx in the coastal group was 1.46 (1.14–1.86) compared to the inland group. According to housing damage, ORs (95% CI) in the no damage, partially destroyed, and more than half destroyed coastal groups compared with the no damage inland group were 1.62 (1.04–2.50), 1.69 (1.17–2.45), and 1.08 (0.71–1.65), respectively. In conclusion, the risk of HTTx withdrawal for participants whose homes in coastal areas were relatively less damaged was significantly higher compared with those in inland areas, while the risk of HTTx withdrawal for participants whose homes were more than half destroyed was not. Post-disaster administrative support for disaster victims is considered vital for continuation of their treatment.

  60. Influence of Diabetes Family History on the Associations of Combined Genetic and Lifestyle Risks with Diabetes in the Tohoku Medical Megabank Community-Based Cohort Study.

    Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Akira Narita, Taku Obara, Mami Ishikuro, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Ichiro Tsuji, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

    Journal of atherosclerosis and thrombosis　2023/10/06

    DOI： 10.5551/jat.64425 　

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    AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

  61. 東日本大震災による家屋損壊の程度と要支援・要介護認定・死亡リスクとの関連

    滑川 千慧, 小暮 真奈, 菅野 郁美, 畑中 里衣子, 中谷 久美, 千葉 一平, 平田 匠, 宇留野 晃, 布施 昇男, 中谷 直樹, 栗山 進一, 寳澤 篤

    日本公衆衛生学会総会抄録集　82回　286-286　2023/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  62. Association Between Olfactory Test Data with Multiple Levels of Odor Intensity and Suspected Cognitive Impairment: A Cross-Sectional Study. International-journal

    Shuichi Sato, Takao Imaeda, Shunji Mugikura, Naoko Mori, Masaki Takanashi, Kazumi Hayakawa, Tomo Saito, Makiko Taira, Akira Narita, Mana Kogure, Ippei Chiba, Rieko Hatanaka, Kumi Nakaya, Ikumi Kanno, Ryosuke Ishiwata, Tomohiro Nakamura, Ikuko N Motoike, Naoki Nakaya, Seizo Koshiba, Kengo Kinoshita, Shinichi Kuriyama, Soichi Ogishima, Fuji Nagami, Nobuo Fuse, Atsushi Hozawa

    Journal of Alzheimer's disease : JAD　2023/09/11

    DOI： 10.3233/JAD-230318 　

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    BACKGROUND: Olfactory function decline has recently been reported to be associated with a risk of cognitive impairment. Few population-based studies have included younger adults when examining the association between olfactory test data with multiple odor intensities and suspected cognitive impairment. OBJECTIVE: We investigated the association between high-resolution olfactory test data with fewer odors and suspected cognitive impairments. We also examined the differences between older and younger adults in this association. METHODS: The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered to 1,450 participants, with three odor-intensity-level olfactometry using six different odors. Logistic regressions to discriminate suspected cognitive impairment were conducted to examine the association, adjusted for age, sex, education duration, and smoking history. Data were collected from the Program by Tohoku University Tohoku Medical Megabank Organization, with an additional olfactory test conducted between 2019 and 2021. RESULTS: We generally observed that the lower the limit of distinguishable odor intensity was, the higher the MoCA-J score was. The combination of spearmint and stuffy socks contributed most to the distinction between suspected and unsuspected cognitive impairment. Furthermore, the association was significant in women aged 60-74 years (adjusted odds ratio 0.881, 95% confidence interval [0.790, 0.983], p = 0.024). CONCLUSIONS: The results indicate an association between the limit of distinguishable odor intensity and cognitive function. The olfactory test with multiple odor intensity levels using fewer odors may be applicable for the early detection of mild cognitive impairment, especially in older women aged 60-74 years.

  63. Associations between birth weight and lung function in a Japanese adult population: The tohoku medical megabank community-based cohort study. International-journal

    Takashi Ohe, Mitsuhiro Yamada, Atsushi Hozawa, Naoki Nakaya, Tomohiro Nakamura, Naho Tsuchiya, Akira Narita, Mana Kogure, Nobuo Fuse, Shinichi Kuriyama, Ayumi Mitsune, Ayumi Suzuki, Shuichiro Matsumoto, Tetsuya Hatakeyama, Chikashi Iwasaki, Manami Suzuki, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Akira Koarai, Tsutomu Tamada, Masayuki Yamamoto, Masakazu Ichinose, Hisatoshi Sugiura

    Respiratory investigation　61　(5)　588-600　2023/07/08

    DOI： 10.1016/j.resinv.2023.06.004 　

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    BACKGROUND: Birth weight, as a measure of intrauterine growth, is commonly used in epidemiological studies and is reported to be associated with adult lung function. However, findings regarding this association in previous studies have been inconsistent. Furthermore, no studies have reported associations stratified by age or smoking status, or adjusted for eosinophil count or other parameters related to type 2 airway inflammation. METHODS: This cross-sectional study included 2632 men and 7237 women aged ≥20 years living in Miyagi Prefecture, Japan. Lung function was assessed based on spirometry. Birth weight data were obtained through a questionnaire survey. Analysis of covariance was used to evaluate the associations between birth weight and lung function, adjusting for potential confounders. Stratified analyses by age and smoking status were also conducted, together with a sub-analysis for low birth-weight participants. RESULTS: Birth weight was positively associated with forced expiratory volume in 1 s (FEV1) for both sexes and with vital capacity in women, after adjusting for height, age, smoking status, and parameters related to type 2 airway inflammation. The stratified analysis for smoking status revealed associations in never-smokers and ex-smokers. When stratified by age, the associations were confirmed in middle-aged participants. The effect of smoking status on the FEV1 of low birth-weight participants was not significant. CONCLUSIONS: Our analysis of a large, Japanese adult population showed that birth weight was independently and positively associated with adult lung function, even after adjustment for age, height, smoking status, and parameters related to type 2 airway inflammation.

  64. Association of Central Blood Pressure and Carotid Intima Media Thickness with New-Onset Hypertension in People with High Normal Blood Pressure.

    Sayuri Tokioka, Naoki Nakaya, Kumi Nakaya, Masato Takase, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Hirohito Metoki, Takahisa Murakami, Michihiro Satoh, Tomohiro Nakamura, Taku Obara, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Junichi Sugawara, Eiichi N Kodama, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

    Journal of atherosclerosis and thrombosis　30　(12)　1905-1916　2023/07/05

    DOI： 10.5551/jat.64151 　

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    AIM: People with high normal blood pressure (BP) have a higher risk of cardiovascular events than those with normal BP; therefore, progression to hypertension (HT) should be prevented. We aimed to assess the HT risk using central BP and carotid intima media thickness (CIMT) in people with high normal BP. METHODS: This prospective cohort study used the Tohoku Medical Megabank Community-Based Project Cohort Study (conducted from 2013 in Miyagi Prefecture in Japan). The participants had a high normal BP, defined as a systolic BP of 120-139 mmHg and diastolic BP ＜90 mmHg using brachial BP measurement during the baseline survey. The outcome was new-onset HT during the secondary survey, conducted four years after the baseline survey. RESULTS: Overall, 4,021 participants with high normal BP during the baseline survey, with an average age of 58.7 years, were included; 1,030 (26%) were diagnosed with new-onset HT during the secondary survey, 3.5± 0.7 years after the baseline survey. The multivariable odds ratio (95% confidence interval) for HT in the highest versus lowest quartile of central BP was 1.7 (1.2-2.4, p=0.0030), and that of CIMT was 1.8 (1.4-2.4, p＜0.001). Subgroup analysis according to age (＜60 and ≥ 60 years) and sex revealed that the central BP was influential in groups with younger age and female individuals; CIMT was influential in all groups. CONCLUSIONS: Higher central BP and thicker CIMT at the baseline were correlated with new-onset HT in individuals with high normal BP, independent of brachial systolic BP and other cardiovascular risk factors.

  65. Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study: Rationale, Design, and Background Peer-reviewed

    Makiko Taira, Shunji Mugikura, Naoko Mori, Atsushi Hozawa, Tomo Saito, Tomohiro Nakamura, Hideyasu Kiyomoto, Tadao Kobayashi, Soichi Ogishima, Fuji Nagami, Akira Uruno, Ritsuko Shimizu, Tomoko Kobayashi, Jun Yasuda, Shigeo Kure, Miyuki Sakurai, Ikuko N. Motoike, Kazuki Kumada, Naoki Nakaya, Taku Obara, Kentaro Oba, Atsushi Sekiguchi, Benjamin Thyreau, Tatsushi Mutoh, Yuji Takano, Mitsunari Abe, Norihide Maikusa, Yasuko Tatewaki, Yasuyuki Taki, Nobuo Yaegashi, Hiroaki Tomita, Kengo Kinoshita, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto

    JMA Journal　6　(3)　246-264　2023/07

    Publisher: Japan Medical Association

    DOI： 10.31662/jmaj.2022-0220 　

    ISSN： 2433-328X

    eISSN： 2433-3298

  66. ゲノムコホート研究参加者5万人を対象としたBRCA1/2遺伝情報の回付と医療への連携

    濱中 洋平, 大根田 絹子, 川目 裕, 布施 昇男, 長神 風二, 鈴木 洋一, 山口 由美, 多田 寛, 原田 成美, 宮下 穣, 江幡 明子, 佐藤 未来, 柳垣 美歌, 山本 雅之, 石田 孝宣

    日本乳癌学会総会プログラム抄録集　31回　89-89　2023/06

    Publisher: (一社)日本乳癌学会

  67. Relationship between age-related hearing loss and consumption of coffee and tea.

    Gosuke Watarai, Jun Suzuki, Ikuko N Motoike, Miyuki Sakurai, Ryoukichi Ikeda, Tetsuaki Kawase, Kengo Kinoshita, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto, Yukio Katori

    Geriatrics & gerontology international　2023/05/03

    DOI： 10.1111/ggi.14589 　

  68. Prevalence, Associated Factors, and Inter-Eye Differences of Refractive Errors in a Population-Based Japanese Cohort: The Tohoku Medical Megabank Eye Study. International-journal

    Atsuya Miki, Nobuo Fuse, Satoko Fujimoto, Makiko Taira, Tomo Saito, Tomoyuki Okazaki, Akihiko Shiraki, Shigeru Sato, Ryo Kawasaki, Tomohiro Nakamura, Kengo Kinoshita, Kohji Nishida, Masayuki Yamamoto

    Ophthalmic epidemiology　1-9　2023/04/24

    DOI： 10.1080/09286586.2023.2203226 　

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    PURPOSE: To investigate the prevalence, associated factors, and inter-eye differences of myopia and astigmatism in an adult Japanese population-based cohort. METHODS: A total of 4282 participants from the Tohoku Medical Megabank Organization Eye Study (ToMMo Eye Study) underwent comprehensive ocular examinations as well as extensive physiological tests and a lifestyle questionnaire. The spherical equivalent (SE) and cylinder power were obtained as refractive parameters. The age- and gender-stratified prevalences of high myopia (SE < -5D), myopia (SE < -0.5D), hyperopia (SE > 0.5D), astigmatism (cylinder power < -0.5D), and anisometropia (SE difference >1D) were calculated. Multivariable analyses were performed to identify associated factors for refractive error (RE). Distribution and associated factors of the inter-eye difference in RE were also investigated. RESULTS: The age-adjusted prevalence of high myopia, myopia, hyperopia, astigmatism, and anisometropia was 15.9%, 63.5%, 14.7%, 51.1%, and 14.7%, respectively. Both myopia and high myopia were more prevalent in the younger age group, while astigmatism was more prevalent in the older age group. Age, education, blood pressure, intraocular pressure, and corneal thickness are significantly associated with myopic refraction. Age, gender, intraocular pressure, and corneal thickness are correlated with astigmatism. Older age was associated with against-the-rule astigmatism. Older age, myopia, and longer education showed a significant correlation with large inter-eye differences in SERE. CONCLUSIONS: This study demonstrated the high prevalence of myopia in young Japanese, which may be caused by a generational shift. This study also confirmed the influence of age and education on both the prevalence and inter-eye differences of RE.

  69. Combined fat mass and fat-free mass indices and lung function among Japanese population: The Tohoku Medical Megabank Community-based Cohort Study.

    Masato Takase, Mitsuhiro Yamada, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

    Journal of epidemiology　2023/04/08

    DOI： 10.2188/jea.JE20220355 　

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    BACKGROUND: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function. METHODS: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s and forced vital capacity was measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1-4 (lowest-highest), and entering the number as a continuous term in the regression model. RESULTS: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV1 (standard deviation) was 3.0 (0.7) L for men and 2.3 (0.5) L for women. The mean FVC was 3.8 (0.7) L for men and 2.8 (0.5) L for women. The FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes. CONCLUSIONS: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.

  70. 心筋ストレスマーカーNT-proBNPと網膜表層血管密度との関連

    橋本 和軌, 國方 彦志, 高田 菜生子, 前川 重人, 二宮 高洋, Sharma Parmanand, 布施 昇男, 麦倉 俊司, 中澤 徹

    日本眼科学会雑誌　127　(臨増)　240-240　2023/03

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  71. Carotid Intima Media Thickness and Risk Factor for Atherosclerosis: Tohoku Medical Megabank Community-Based Cohort Study.

    Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

    Journal of atherosclerosis and thrombosis　2023/02/11

    DOI： 10.5551/jat.64039 　

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    AIM: We examined the association between the carotid intima medica thickness (cIMT) and risk factors for atherosclerosis based on the Japan Atherosclerosis Society 2022 Atherosclerosis Prevention Guideline. METHODS: Using data from the Tohoku Medical Megabank Community-based Cohort Study, we performed a cross-sectional study that enrolled 13,366 participants (age ≥ 20 years) with an analysis of covariance to assess associations between cIMT and risk factors for atherosclerosis. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. Analysis was conducted in the model adjusted for age, sex, smoking status, drinking status, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), high-density lipoprotein-cholesterol (HDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and height. RESULTS: In this study cohort, the average age and cIMT were 57.3 (13.8) years and 0.61 (0.13) mm, respectively, which included 3,988 males (29.8%). Males had a higher cIMT than did the females. Age, height, BMI, SBP, HbA1c, and non-HDL-C were positively associated with cIMT. HDL-C was inversely associated with cIMT. Compared with never drinkers, current drinkers (≥ 46.0 g/day) had a significantly decreased cIMT. CONCLUSIONS: The cIMT was associated with atherosclerosis risk factors including age, sex, BMI, SBP, HbA1c, non-HDL-C, and HDL-C, and adequate control of risks in high-risk individuals might be required to prevent atherosclerotic cardiovascular diseases.

  72. 脂肪量指数と除脂肪量指数の組み合わせと呼吸機能検査指標の関連

    高瀬 雅仁, 山田 充啓, 中村 智洋, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 菅野 郁美, 布施 昇男, 栗山 進一, 辻 一郎, 寳澤 篤

    Journal of Epidemiology　33　(Suppl.1)　155-155　2023/02

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  73. 糖尿病指標と嗅覚機能の関連

    佐竹 芽久美, 菅野 郁美, 佐藤 守一, 今枝 孝夫, 高梨 昌樹, 早川 和美, 中谷 久美, 千葉 一平, 小暮 真奈, 畑中 里衣子, 斉藤 智, 中村 智洋, 長神 風二, 荻島 創一, 布施 昇男, 麦倉 俊司, 栗山 進一, 中谷 直樹, 寳澤 篤

    Journal of Epidemiology　33　(Suppl.1)　156-156　2023/02

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  74. 東北メディカル・メガバンク計画地域住民コホート調査(宮城)詳細二次調査の概要

    中谷 久美, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 千葉 一平, 菅野 郁美, 中村 智洋, 小原 拓, 宇留野 晃, 布施 昇男, 辻 一郎, 栗山 進一, 寳澤 篤

    Journal of Epidemiology　33　(Suppl.1)　173-173　2023/02

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  75. Exome sequencing reveals that the CYP1B1 and FOXC1 genes are mainly responsible for childhood glaucoma in Japanese patients

    Nobuo Fuse, Masae Kimura, Ai Shimizu, Teruhiko Hamanaka, Makoto Nakamura, Nobuo Ishida, Hiroshi Sakai, Yoko Ikeda, Kazuhiko Mori, Atsushi Endo, Masao nagasaki, Fumiki Katsuoka, Jun Yasuda, Yoichi Matsubara, Toru Nakazawa, Masayuki Yamamoto

    2023/01/12

    DOI： 10.21203/rs.3.rs-2445970/v1 　

  76. Association between lung function and hypertension and home hypertension in a Japanese population: the Tohoku Medical Megabank Community-Based Cohort Study. International-journal Peer-reviewed

    Masato Takase, Mitsuhiro Yamada, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

    Journal of hypertension　41　(3)　443-52　2023/01/04

    DOI： 10.1097/HJH.0000000000003356 　

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    BACKGROUND: Although several studies have shown an inverse association between lung function and hypertension, few studies have examined the association between lung function and hypertension among never-smokers, and no study has investigated the association between lung function and home hypertension. We investigated the associations between lung function and hypertension in a Japanese population. INDIVIDUALS AND METHODS: We conducted a cross-sectional study of 3728 men and 8795 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was assessed using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), measured by spirometry. Hypertension was defined as a casual blood pressure at least 140/90 mmHg and/or self-reported treatment for hypertension. Home hypertension was defined as morning home blood pressure at least 135/85 mmHg and/or self-reported treatment for hypertension. Multivariate logistic regression models adjusted for potential confounders were used to assess the association between lung function and hypertension. RESULTS: The mean ages (±SD) of men and women were 60.1 (±14.0) years and 56.2 (±13.4) years, respectively, and 1994 (53.5%) men and 2992 (34.0%) women had hypertension. In the multivariable models, FEV1 and FVC were inversely associated with hypertension. Inverse associations between lung function and hypertension were observed even among never-smokers. Furthermore, reduced lung function was associated with higher prevalence of home hypertension in men and women. CONCLUSION: Reduced lung function was associated with higher prevalence of hypertension, independent of smoking status. Assessment of the lung function or blood pressure may be required in individuals with reduced lung function or hypertension.

  77. Comprehensive evaluation of machine learning algorithms for predicting sleep-wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability. International-journal

    Xue Li, Chiaki Ono, Noriko Warita, Tomoka Shoji, Takashi Nakagawa, Hitomi Usukura, Zhiqian Yu, Yuta Takahashi, Kei Ichiji, Norihiro Sugita, Natsuko Kobayashi, Saya Kikuchi, Ryoko Kimura, Yumiko Hamaie, Mizuki Hino, Yasuto Kunii, Keiko Murakami, Mami Ishikuro, Taku Obara, Tomohiro Nakamura, Fuji Nagami, Takako Takai, Soichi Ogishima, Junichi Sugawara, Tetsuro Hoshiai, Masatoshi Saito, Gen Tamiya, Nobuo Fuse, Susumu Fujii, Masaharu Nakayama, Shinichi Kuriyama, Masayuki Yamamoto, Nobuo Yaegashi, Noriyasu Homma, Hiroaki Tomita

    Frontiers in psychiatry　14　1104222-1104222　2023

    DOI： 10.3389/fpsyt.2023.1104222 　

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    INTRODUCTION: Perinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep-wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV). METHODS: Nine HRV indicators (features) and sleep-wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep-wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated-shallow sleep, deep sleep, and the two types of wake conditions-was also tested. RESULTS AND DISCUSSION: In the test for predicting three types of sleep-wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82-0.88) and accuracy (0.78-0.81). The test using four types of sleep-wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep-wake conditions. Among the seven features, "the number of interval differences of successive RR intervals greater than 50 ms (NN50)" and "the proportion dividing NN50 by the total number of RR intervals (pNN50)" were useful to predict sleep-wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy.

  78. The Association of Lung Function and Carotid Intima-Media Thickness in a Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

    Masato Takase, Mitsuhiro Yamada, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

    Journal of atherosclerosis and thrombosis　2022/11/04

    DOI： 10.5551/jat.63826 　

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    AIM: Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population. METHODS: We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model. RESULTS: After adjusting for potential confounders including passive smoking, lower FEV1 and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years). CONCLUSIONS: Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.

  79. Pathological variants in genes associated with disorders of sex development and central causes of hypogonadism in a whole-genome reference panel of 8380 Japanese individuals. International-journal

    Naomi Shiga, Yumi Yamaguchi-Kabata, Saori Igeta, Jun Yasuda, Shu Tadaka, Takamichi Minato, Zen Watanabe, Junko Kanno, Gen Tamiya, Nobuo Fuse, Kengo Kinoshita, Shigeo Kure, Akiko Kondo, Masahito Tachibana, Masayuki Yamamoto, Nobuo Yaegashi, Junichi Sugawara

    Human genome variation　9　(1)　34-34　2022/09/28

    DOI： 10.1038/s41439-022-00213-w 　

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    Disorders of sex development (DSD) comprises a congenital condition in which chromosomal, gonadal, or anatomical sex development is atypical. In this study, we screened for pathogenic variants in 32 genes associated with DSDs and central causes of hypogonadism (CHG) in a whole-genome reference panel including 8380 Japanese individuals constructed by Tohoku Medical Megabank Organization. Candidate pathogenic (P) or likely pathogenic (LP) variants were extracted from the ClinVar, InterVar, and Human Gene Mutation databases. Ninety-one candidate pathological variants were found in 25 genes; 28 novel candidate variants were identified. Nearly 1 in 40 (either ClinVar or InterVar P or LP) to 157 (both ClinVar and InterVar P or LP) individuals were found to be carriers of recessive DSD and CHG alleles. In these data, genes implicated in gonadal dysfunction did not show loss-of-function variants, with a relatively high tendency of intolerance for haploinsufficiency based on pLI and Episcore, both of which can be used for estimating haploinsufficiency. We report the types and frequencies of causative variants for DSD and CHG in the general Japanese population. This study furthers our understanding of the genetic causes and helps to refine genetic counseling of DSD and CHG.

  80. Returning individual genomic results to population-based cohort study participants with BRCA1/2 pathogenic variants.

    Kinuko Ohneda, Yohei Hamanaka, Hiroshi Kawame, Nobuo Fuse, Fuji Nagami, Yoichi Suzuki, Yumi Yamaguchi-Kabata, Muneaki Shimada, Atsushi Masamune, Yoko Aoki, Takanori Ishida, Masayuki Yamamoto

    Breast cancer (Tokyo, Japan)　30　(1)　110-120　2022/09/26

    DOI： 10.1007/s12282-022-01404-7 　

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    BACKGROUND: Recent advances in human genome research have provided evidence for genotype-phenotype associations, pathogenicity, and clinical actionability of variants and genomic risk prediction of disease. However, the return of individual genomic results to healthy individuals is fraught with ethical and practical complexity. METHODS: Individual genomic results were returned to BRCA1/2 pathogenic variant (PV) carriers of the Tohoku Medical Megabank cohort study participants with an information on hereditary breast and ovarian cancer syndrome (HBOC). One hundred and eighty participants, including 9 BRCA1/2 PV carriers, were asked about their willingness to receive individual genomic results, without revealing the gene name and related disorders, prior to the study. Of the 142 participants who responded, 103 showed willingness to know their genomic information. Each of the six BRCA1/2 PV carriers who consented to participate in the study received information about HBOC in person and underwent validation testing with blood resampling. RESULTS: All participants were in their 60s or 70s; of the four females and two males, two had a history of breast cancer and five had a family history of HBOC-related cancers. All participants appreciated the information, without remarkable negative psychological impact of the return, and intended to undergo clinical risk surveillance. Five participants were accompanied by family members while receiving the results, and three first-degree female relatives wished to undergo genomic testing at the hospital. CONCLUSIONS: Our results suggest that returning actionable genomic information to participants in a population-based genome cohort study is beneficial for preventing or providing early-stage intervention for associated diseases.

  81. 呼吸機能検査指標と高血圧有病との関連

    高瀬 雅仁, 山田 充啓, 中村 智洋, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 菅野 郁美, 土屋 菜歩, 平田 匠, 布施 昇男, 栗山 進一, 辻 一郎, 寳澤 篤

    日本公衆衛生学会総会抄録集　81回　202-202　2022/09

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  82. 東日本大震災による自宅の被害状況と高血圧治療中断との関連

    畑中 里衣子, 中谷 直樹, 小暮 真奈, 中谷 久美, 千葉 一平, 菅野 郁美, 中村 智洋, 後岡 広太郎, 小原 拓, 布施 昇男, 栗山 進一, 辻 一郎, 寳澤 篤

    日本公衆衛生学会総会抄録集　81回　196-196　2022/09

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  83. 握力および脚伸展力で測定した各筋力と生理学的データの関連

    野路 慶明, 畑中 里衣子, 中谷 直樹, 小暮 真奈, 中谷 久美, 千葉 一平, 菅野 郁美, 中村 智洋, 布施 昇男, 栗山 進一, 辻 一郎, 寳澤 篤

    日本公衆衛生学会総会抄録集　81回　431-431　2022/09

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  84. 全ゲノム/全エキソーム解析による生殖細胞系列多型の探索 一般住民コホートにおけるBRCA遺伝子バリアントの探索及び結果の回付事業について(Exploration of BRCA1/2 gene variants in a general population cohort and return of genomic results to the participants)

    徳永 英樹, 安田 純, 島田 宗昭, 濱中 洋平, 重田 昌吾, 布施 昇男, 勝岡 史城, 荻島 創一, 山口 由美, 寳澤 篤, 川目 裕, 大根田 絹子, 青木 洋子, 山本 雅之, 八重樫 伸生

    日本癌学会総会記事　81回　S8-1　2022/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  85. 呼吸機能検査指標と高血圧有病との関連

    高瀬 雅仁, 山田 充啓, 中村 智洋, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 菅野 郁美, 土屋 菜歩, 平田 匠, 布施 昇男, 栗山 進一, 辻 一郎, 寳澤 篤

    日本公衆衛生学会総会抄録集　81回　202-202　2022/09

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  86. 東北メディカル・メガバンク計画・地域住民コホート調査詳細三次調査(宮城)の進捗

    中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 菅野 郁美, 小原 拓, 中村 智洋, 宇留野 晃, 布施 昇男, 泉 陽子, 丹野 高三, 辻 一郎, 栗山 進一, 寳澤 篤

    東北公衆衛生学会誌　(71)　28-28　2022/07

    Publisher: 東北公衆衛生学会

    ISSN： 0915-549X

  87. Associations between the Combined Fat Mass Index and Fat-Free Mass Index with Carotid Intima-Media Thickness in a Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

    Masato Takase, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Kichiya Suzuki, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hozawa

    Journal of atherosclerosis and thrombosis　30　(3)　255-273　2022/05/26

    DOI： 10.5551/jat.63523 　

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    AIM: Although many epidemiological studies have shown that obesity assessed by body mass index is associated with carotid intima-media thickness (cIMT), few studies have evaluated fat-free mass, which is a component of body composition. We investigated the associations between the combined fat mass index (FMI) and fat-free mass index (FFMI) with cIMT. METHODS: We conducted a cross-sectional study of 3,873 men and 9,112 women aged 20 years or older who lived in Miyagi prefecture, Japan. The FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. The indices were classified into sex-specific quartiles and were combined into 16 groups. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between the combined FMI and FFMI with cIMT adjusted for age and smoking status. The linear trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1 (lowest) to 4 (highest), and entering the number as a continuous term in the regression model. RESULTS: In multivariable models, a higher FMI was not related to higher cIMT in men and women in most FFMI subgroups. Conversely, a higher FFMI was related to higher cIMT in all FMI subgroups (p＜0.001 for linear trend). CONCLUSIONS: FMI was not associated with cIMT in most FFMI subgroups. Conversely, FFMI was positively associated with cIMT independently of FMI.

  88. Association between fat mass index, fat-free mass index and hemoglobin A1c in a Japanese population: The Tohoku Medical Megabank Community-based Cohort Study.

    Masato Takase, Tomohiro Nakamura, Takumi Hirata, Naho Tsuchiya, Mana Kogure, Fumi Itabashi, Naoki Nakaya, Yohei Hamanaka, Junichi Sugawara, Kichiya Suzuki, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hozawa

    Journal of diabetes investigation　13　(5)　858-867　2022/05

    DOI： 10.1111/jdi.13729 　

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    AIMS/INTRODUCTION: Fat mass and fat-free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat-free mass index with HbA1c. MATERIALS AND METHODS: We carried out a cross-sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat-free mass index were calculated as fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into sex-specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat-free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat-free mass index, entering the number as a continuous term in the regression model. RESULTS: In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat-free mass index subgroups (P < 0.001 for linear trend). When we excluded the participants who had been identified as having diabetes, the fat-free mass index was also related to higher HbA1c levels in most fat mass index subgroups (P < 0.05 for linear trend). CONCLUSIONS: Fat mass index was positively related to HbA1c levels. The fat-free mass index was also related to HbA1c levels when we excluded participants who had been identified as having have diabetes.

  89. A Pilot Study for Return of Individual Pharmacogenomic Results to Population-Based Cohort Study Participants.

    Kinuko Ohneda, Masahiro Hiratsuka, Hiroshi Kawame, Fuji Nagami, Yoichi Suzuki, Kichiya Suzuki, Akira Uruno, Mika Sakurai-Yageta, Yohei Hamanaka, Makiko Taira, Soichi Ogishima, Shinichi Kuriyama, Atsushi Hozawa, Hiroaki Tomita, Naoko Minegishi, Junichi Sugawara, Inaho Danjoh, Tomohiro Nakamura, Tomoko Kobayashi, Yumi Yamaguchi-Kabata, Shu Tadaka, Taku Obara, Eiji Hishimuma, Nariyasu Mano, Masaki Matsuura, Yuji Sato, Masateru Nakasone, Yohei Honkura, Jun Suzuki, Yukio Katori, Yoichi Kakuta, Atsushi Masamune, Yoko Aoki, Masaharu Nakayama, Shigeo Kure, Kengo Kinoshita, Nobuo Fuse, Masayuki Yamamoto

    JMA journal　5　(2)　177-189　2022/04/15

    DOI： 10.31662/jmaj.2021-0156 　

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    Introduction: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings. Methods: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1, CYP2C19, and NUDT15, were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants' understanding of the topic, psychological impact, and attitude toward the study. Results: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable. Conclusions: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting.

  90. 東北メディカル・メガバンク計画健康調査における眼軸長のゲノムワイド関連解析

    布施 昇男, 櫻井 美由紀, 元池 育子, 小島 要, 平良 摩紀子, 宇留野 晃, 濱中 洋平, 中村 智洋, 荻島 創一, 寳澤 篤, 栗山 進一, 呉 繁夫, 木下 賢吾, 山本 雅之

    日本眼科学会雑誌　126　(臨増)　216-216　2022/03

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  91. Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan

    Nobuo Fuse, Miyuki Sakurai, Ikuko N. Motoike, Kaname Kojima, Takako Takai-Igarashi, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Akiko Miyazawa, Kei Homma, Keisuke Ido, Makiko Taira, Tomoko Kobayashi, Ritsuko Shimizu, Akira Uruno, Eiichi N. Kodama, Kichiya Suzuki, Yohei Hamanaka, Hiroaki Tomita, Junichi Sugawara, Yoichi Suzuki, Fuji Nagami, Soichi Ogishima, Fumiki Katsuoka, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Yaegashi, Shigeo Kure, Kengo Kinoshita, Masayuki Yamamoto

    Ophthalmology Science　2　(1)　100113-100113　2022/03

    Publisher: Elsevier BV

    DOI： 10.1016/j.xops.2022.100113 　

    ISSN： 2666-9145

  92. 東北メディカル・メガバンク計画・地域住民コホート調査詳細三次調査(宮城)の進捗

    中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 菅野 郁美, 小原 拓, 中村 智洋, 宇留野 晃, 布施 昇男, 泉 陽子, 丹野 高三, 辻 一郎, 栗山 進一, 呉 繁夫, 寳澤 篤

    Journal of Epidemiology　32　(Suppl.1)　162-162　2022/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  93. dbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project. International-journal

    Soichi Ogishima, Satoshi Nagaie, Satoshi Mizuno, Ryosuke Ishiwata, Keita Iida, Kazuro Shimokawa, Takako Takai-Igarashi, Naoki Nakamura, Sachiko Nagase, Tomohiro Nakamura, Naho Tsuchiya, Naoki Nakaya, Keiko Murakami, Fumihiko Ueno, Tomomi Onuma, Mami Ishikuro, Taku Obara, Shunji Mugikura, Hiroaki Tomita, Akira Uruno, Tomoko Kobayashi, Akito Tsuboi, Shu Tadaka, Fumiki Katsuoka, Akira Narita, Mika Sakurai, Satoshi Makino, Gen Tamiya, Yuichi Aoki, Ritsuko Shimizu, Ikuko N Motoike, Seizo Koshiba, Naoko Minegishi, Kazuki Kumada, Takahiro Nobukuni, Kichiya Suzuki, Inaho Danjoh, Fuji Nagami, Kozo Tanno, Hideki Ohmomo, Koichi Asahi, Atsushi Shimizu, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Teiji Tominaga, Shigeo Kure, Nobuo Yaegashi, Kengo Kinoshita, Makoto Sasaki, Hiroshi Tanaka, Masayuki Yamamoto

    Human genome variation　8　(1)　44-44　2021/12/10

    DOI： 10.1038/s41439-021-00175-5 　

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    To reveal gene-environment interactions underlying common diseases and estimate the risk for common diseases, the Tohoku Medical Megabank (TMM) project has conducted prospective cohort studies and genomic and multiomics analyses. To establish an integrated biobank, we developed an integrated database called "dbTMM" that incorporates both the individual cohort/clinical data and the genome/multiomics data of 157,191 participants in the Tohoku Medical Megabank project. To our knowledge, dbTMM is the first database to store individual whole-genome data on a variant-by-variant basis as well as cohort/clinical data for over one hundred thousand participants in a prospective cohort study. dbTMM enables us to stratify our cohort by both genome-wide genetic factors and environmental factors, and it provides a research and development platform that enables prospective analysis of large-scale data from genome cohorts.

  94. Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator

    Mitsuhiro Yamada, Ikuko N. Motoike, Kaname Kojima, Nobuo Fuse, Atsushi Hozawa, Shinichi Kuriyama, Fumiki Katsuoka, Shu Tadaka, Matsuyuki Shirota, Miyuki Sakurai, Tomohiro Nakamura, Yohei Hamanaka, Kichiya Suzuki, Junichi Sugawara, Soichi Ogishima, Akira Uruno, Eiichi N. Kodama, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Ayumi Mitsune, Takashi Ohe, Kengo Kinoshita, Masakazu Ichinose, Hisatoshi Sugiura, Masayuki Yamamoto

    Communications Biology　4　(1)　2021/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s42003-021-02813-8 　

    eISSN： 2399-3642

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    <title>Abstract</title>Lung function reflects the ability of the respiratory system and is utilized for the assessment of respiratory diseases. Because type 2 airway inflammation influences lung function, genome wide association studies (GWAS) for lung function would be improved by adjustment with an indicator of the inflammation. Here, we performed a GWAS for lung function with adjustment for exhaled nitric oxide (FeNO) levels in two independent Japanese populations. Our GWAS with genotype imputations revealed that the <italic>RNF5/AGER</italic> locus including <italic>AGER</italic> rs2070600 SNP, which introduces a G82S substitution of AGER, was the most significantly associated with FEV1/FVC. Three other rare missense variants of AGER were further identified. We also found genetic loci with three candidate genes (<italic>NOS2, SPSB2</italic> and <italic>RIPOR2</italic>) associated with FeNO levels. Analyses with the BioBank-Japan GWAS resource revealed genetic links of FeNO and asthma-related traits, and existence of common genetic background for allergic diseases and their biomarkers. Our study identified the genetic locus most strongly associated with airway obstruction in the Japanese population and three genetic loci associated with FeNO, an indicator of type 2 airway inflammation in adults.

  95. 東北メディカル・メガバンク計画・地域住民コホート調査詳細三次調査(宮城)の概要

    中谷 直樹, 小暮 真奈, 畑中 里衣子, 菅野 郁美, 中谷 久美, 小原 拓, 中村 智洋, 宇留野 晃, 布施 昇男, 泉 陽子, 丹野 高三, 辻 一郎, 栗山 進一, 呉 繁夫, 寳澤 篤

    日本公衆衛生学会総会抄録集　80回　219-219　2021/11

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  96. Association between the combined fat mass and fat-free mass index and hypertension: The Tohoku Medical Megabank Community-based Cohort Study. International-journal

    Masato Takase, Tomohiro Nakamura, Naho Tsuchiya, Mana Kogure, Fumi Itabashi, Akira Narita, Takumi Hirata, Naoki Nakaya, Yohei Hamanaka, Junichi Sugawara, Kichiya Suzuki, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hozawa

    Clinical and experimental hypertension (New York, N.Y. : 1993)　43　(7)　610-621　2021/10/03

    DOI： 10.1080/10641963.2021.1925681 　

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    BACKGROUND: A  higher body fat percentage is associated with hypertension, even in non-obese individuals. The difference in body composition may be related to hypertension. The fat mass index (FMI) and fat-free mass index (FFMI) are proposed indicators of body composition. This study aimed to examine the relationship of a combination of FMI and FFMI with hypertension. METHODS: We conducted a cross-sectional study of 5,058 men and 11,842 women aged ≥ 20 years in the Miyagi Prefecture, northeastern Japan. The FMI and FFMI were calculated as the fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into quartiles and combined into 16 groups. Hypertension was defined as casual blood pressure ≥ 140/90 mmHg and/or self-reported treatment for hypertension. Multivariable logistic regression models, adjusted for potential confounders, were used to assess the relationship of a combination of FMI and FFMI with hypertension. RESULTS: Higher FMI was associated with hypertension in most of the FFMI subgroups. Similarly, a higher FFMI was associated with hypertension in most of FMI subgroups. For men, the association between FFMI and hypertension in the lowest FMI group was not significant. CONCLUSIONS: Reducing the FMI and FFMI may be important in preventing hypertension. For men, the relationship between the FFMI and hypertension in the lowest FMI group might be weak.

  97. Comparisons of Schlemm's canal and trabecular meshwork morphologies between juvenile and primary open angle glaucoma. International-journal

    Teruhiko Hamanaka, Tetsuro Sakurai, Nobuo Fuse, Nobuo Ishida, Toshio Kumasaka, Masaki Tanito

    Experimental eye research　210　108711-108711　2021/08/02

    DOI： 10.1016/j.exer.2021.108711 　

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    The histologic differences in Schlemm's canal (SC) and trabecular meshwork (TM), obtained from the trabeculectomy specimens of different age-group glaucoma patients, were compared. This study involved 44 trabeculectomy specimens of 37 juvenile-onset open-angle glaucoma (JOAG) patients (Group A) and 24 trabeculectomy specimens of 24 elderly-onset primary OAG (POAG) patients (age range: 70-79 years, Group B) with no familial history of POAG. Clinical parameters of gender, maximum intraocular pressure (IOP), and the number of glaucoma medications used prior to trabeculectomy were investigated and compared between the two groups. From light microscopy photographs of hematoxylin-eosin, and immunohistochemical staining of markers for SC endothelium (SCE), the total SC length (TSC), comprised of the opened-SC length (OSC) and the closed-SC length (CSC), the percentage of CSC in TSC (%CSC), the percentage of positive SCE marker in CSC (%PinCSC), and the percentage of negative SCE marker in OSC (%NinOSC) were analyzed. Moreover, podoplanin staining patterns in the TM were investigated and compared between the two groups. Among the clinical parameters, the mean maximum IOP in Group A (33.41 ± 9.24 mmHg) was the only significant parameter when compared to that in Group B (22.96 ± 7.17 mmHg, P = 0.000003). TSC in Group A was significantly shorter than that in Group B (P = 0.00092), and %CSC (P = 0.00004) and %PinCSC (P = 0.00342) in Group B were significantly higher than those in Group A. No statistically significant difference in %NinOSC was found between Group A and Group B (P = 0.76060). Juxtacanalicular tissue (JCT) in Group A showed compact and weak staining with podoplanin, while the JCT and closed-SC area in Group B showed intense staining. In the Group A subjects, TSC (P = 0.04819) and OSC (P = 0.02867) were significantly shorter in the non-familial cases than in the familial cases. Platelet coagulations 10-37 μm in size at the defect of the SCE in the inner wall of the SC were observed in 8 eyes (18%) and 4 eyes (17%) in Group A and Group B, respectively. The platelets appeared to repair the SCE damage for maintaining the blood aqueous barrier in both groups of POAG eyes. Smaller SC diameters and accompanying TM abnormality were features observed in the young-onset JOAG patients, thus suggesting developmental abnormalities in the outflow routes. The collapse of SC lumen, presumably due to aging, was the feature observed in the elderly-onset POAG patients. In Group A, the significantly higher IOP, despite of no significant number of topical medications used prior to trabeculectomy, also suggested that JOAG eyes can be categorized as a distinct type of POAG from the eyes of elder-aged POAG patients. The SCE drop out observed in the glaucomatous eyes of the different age groups suggested that worsening of IOP control may possibly occur equally in both groups.

  98. The return of individual genomic results to research participants: design and pilot study of Tohoku Medical Megabank Project. International-journal

    Hiroshi Kawame, Akimune Fukushima, Nobuo Fuse, Fuji Nagami, Yoichi Suzuki, Mika Sakurai-Yageta, Jun Yasuda, Yumi Yamaguchi-Kabata, Kengo Kinoshita, Soichi Ogishima, Takako Takai, Shinichi Kuriyama, Atsushi Hozawa, Naoki Nakaya, Tomohiro Nakamura, Naoko Minegishi, Junichi Sugawara, Kichiya Suzuki, Hiroaki Tomita, Akira Uruno, Tomoko Kobayashi, Yayoi Aizawa, Tomoharu Tokutomi, Kayono Yamamoto, Kinuko Ohneda, Shigeo Kure, Yoko Aoki, Hideki Katagiri, Yasushi Ishigaki, Shojiro Sawada, Makoto Sasaki, Masayuki Yamamoto

    Journal of human genetics　67　(1)　9-17　2021/07/08

    DOI： 10.1038/s10038-021-00952-8 　

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    Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results, we extracted the potential challenges and obstacles. Major challenges include the determination of genes/disorders based on the current medical system in Japan, the storage of results, prevention of misunderstanding, and collaboration of medical professionals. To overcome these challenges, we plan to conduct multilayer pilot studies, which deal with different disorders/genes. We finally chose familial hypercholesterolemia (FH) as a target disease for the first pilot study. Of the 665 eligible candidates, 33.5% were interested in the pilot study and provided consent after an educational "genetics workshop" on the basic genetics and medical facts of FH. The genetics professionals disclosed the results to the participants. All positive participants were referred to medical care, and a serial questionnaire revealed no significant psychosocial distress after the disclosure. Return of genomic results to research participants was implemented using a well-prepared protocol. To further elucidate the impact of different disorders, we will perform multilayer pilot studies with different disorders, including actionable pharmacogenomics and hereditary tumor syndromes.

  99. ゲノムコホート研究におけるBRCA1/2遺伝情報返却とその後の医療機関との連携の取組み

    濱中 洋平, 多田 寛, 宮下 穣, 原田 成美, 佐藤 章子, 江幡 明子, 大根田 絹子, 布施 昇男, 川目 裕, 鈴木 洋一, 長神 風二, 鈴木 吉也, 佐藤 政文, 平塚 真弘, 櫻井 美佳, 宇留野 晃, 山口 由美, 平良 摩紀子, 山本 雅之, 石田 孝宣

    日本乳癌学会総会プログラム抄録集　29回　21-21　2021/07

    Publisher: (一社)日本乳癌学会

  100. ゲノムコホート研究におけるBRCA1/2遺伝情報返却とその後の医療機関との連携の取組み

    濱中 洋平, 多田 寛, 宮下 穣, 原田 成美, 佐藤 章子, 江幡 明子, 大根田 絹子, 布施 昇男, 川目 裕, 鈴木 洋一, 長神 風二, 鈴木 吉也, 佐藤 政文, 平塚 真弘, 櫻井 美佳, 宇留野 晃, 山口 由美, 平良 摩紀子, 山本 雅之, 石田 孝宣

    日本乳癌学会総会プログラム抄録集　29回　21-21　2021/07

    Publisher: (一社)日本乳癌学会

  101. Japonica Array NEO with increased genome-wide coverage and abundant disease risk SNPs

    Mika Sakurai-Yageta, Kazuki Kumada, Chinatsu Gocho, Satoshi Makino, Akira Uruno, Shu Tadaka, Ikuko N Motoike, Masae Kimura, Shin Ito, Akihito Otsuki, Akira Narita, Hisaaki Kudo, Yuichi Aoki, Inaho Danjoh, Jun Yasuda, Hiroshi Kawame, Naoko Minegishi, Seizo Koshiba, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

    The Journal of Biochemistry　2021/05/13

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/jb/mvab060 　

    ISSN： 0021-924X

    eISSN： 1756-2651

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    <title>Abstract</title> Ethnic-specific SNP arrays are becoming more important to increase the power of genome-wide association studies in diverse population. In the Tohoku Medical Megabank Project, we have been developing a series of Japonica Arrays (JPA) for genotyping participants based on reference panels constructed from whole-genome sequence data of the Japanese population. Here, we designed a novel version of the SNP array for the Japanese population, called Japonica Array NEO (JPA NEO), comprising a total of 666,883 markers. Among them, 654,246 tag SNPs of autosomes and X chromosome were selected from an expanded reference panel of 3,552 Japanese, 3.5KJPNv2, using pairwise r2 of linkage disequilibrium measures. Additionally, 28,298 markers were included for the evaluation of previously identified disease risk markers from the literature and databases, and those present in the Japanese population were extracted using the reference panel. Through genotyping 286 Japanese samples, we found that the imputation quality r2 and INFO score in the minor allele frequency bin &amp;gt;2.5–5% were &amp;gt;0.9 and &amp;gt;0.8, respectively, and &amp;gt;12 million markers were imputed with an INFO score &amp;gt;0.8. From these results, JPA NEO is a promising tool for genotyping the Japanese population with genome-wide coverage, contributing to the development of genetic risk scores.

  102. Estimation of the carrier frequencies and proportions of potential patients by detecting causative gene variants associated with autosomal recessive bone dysplasia using a whole-genome reference panel of Japanese individuals. International-journal

    Shinichi Nagaoka, Yumi Yamaguchi-Kabata, Naomi Shiga, Masahito Tachibana, Jun Yasuda, Shu Tadaka, Gen Tamiya, Nobuo Fuse, Kengo Kinoshita, Shigeo Kure, Jun Murotsuki, Masayuki Yamamoto, Nobuo Yaegashi, Junichi Sugawara

    Human genome variation　8　(1)　2-2　2021/01/15

    DOI： 10.1038/s41439-020-00133-7 　

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    Bone dysplasias are a group of rare hereditary diseases, with up to 436 disease types. Perinatal diagnosis is clinically important for adequate personalized management and counseling. There are no reports focused on pathogenic variants of bone dysplasias in the general population. In this study, we focused on autosomal recessive bone dysplasias. We identified pathogenic variants using whole-genome reference panel data from 3552 Japanese individuals. For the first time, we were able to estimate the carrier frequencies and the proportions of potential patients. For autosomal recessive bone dysplasias, we detected 198 pathogenic variants of 54 causative genes. We estimated the variant carrier frequencies and the proportions of potential patients with variants associated with four clinically important bone dysplasias: osteogenesis imperfecta (OI), hypophosphatasia (HPP), asphyxiating thoracic dysplasia (ATD), and Ellis-van Creveld syndrome (EvC). The proportions of potential patients with OI, ATD, and EvC based on pathogenic variants classified as "pathogenic" and "likely pathogenic" by InterVar were closer to the reported incidence rates in Japanese subjects. Furthermore, the proportions of potential patients with HPP variants classified as "pathogenic" and "likely pathogenic" in InterVar and "pathogenic" in ClinVar were closer to the reported incidence rates. For bone dysplasia, the findings of this study will provide a better understanding of the variant types and frequencies in the Japanese general population, and should be useful for clinical diagnosis, genetic counseling, and personalized medicine.

  103. Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study.

    Atsushi Hozawa, Kozo Tanno, Naoki Nakaya, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Akira Narita, Mana Kogure, Kotaro Nochioka, Ryohei Sasaki, Nobuyuki Takanashi, Kotaro Otsuka, Kiyomi Sakata, Shinichi Kuriyama, Masahiro Kikuya, Osamu Tanabe, Junichi Sugawara, Kichiya Suzuki, Yoichi Suzuki, Eiichi N Kodama, Nobuo Fuse, Hideyasu Kiyomoto, Hiroaki Tomita, Akira Uruno, Yohei Hamanaka, Hirohito Metoki, Mami Ishikuro, Taku Obara, Tomoko Kobayashi, Kazuyuki Kitatani, Takako Takai-Igarashi, Soichi Ogishima, Mamoru Satoh, Hideki Ohmomo, Akito Tsuboi, Shinichi Egawa, Tadashi Ishii, Kiyoshi Ito, Sadayoshi Ito, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Masao Nagasaki, Kazuhiko Igarashi, Seizo Koshiba, Ritsuko Shimizu, Gen Tamiya, Keiko Nakayama, Hozumi Motohashi, Jun Yasuda, Atsushi Shimizu, Tsuyoshi Hachiya, Yuh Shiwa, Teiji Tominaga, Hiroshi Tanaka, Kotaro Oyama, Ryoichi Tanaka, Hiroshi Kawame, Akimune Fukushima, Yasushi Ishigaki, Tomoharu Tokutomi, Noriko Osumi, Tadao Kobayashi, Fuji Nagami, Hiroaki Hashizume, Tomohiko Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Ryujin Endo, Satoshi Nishizuka, Ichiro Tsuji, Jiro Hitomi, Motoyuki Nakamura, Kuniaki Ogasawara, Nobuo Yaegashi, Kengo Kinoshita, Shigeo Kure, Akio Sakai, Seiichiro Kobayashi, Kenji Sobue, Makoto Sasaki, Masayuki Yamamoto

    Journal of epidemiology　31　(1)　65-76　2021/01/05

    DOI： 10.2188/jea.JE20190271 　

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    BACKGROUND: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases. METHODS: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely. RESULTS: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex. CONCLUSION: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

  104. Heart Rate Information-Based Machine Learning Prediction of Emotions Among Pregnant Women. International-journal

    Xue Li, Chiaki Ono, Noriko Warita, Tomoka Shoji, Takashi Nakagawa, Hitomi Usukura, Zhiqian Yu, Yuta Takahashi, Kei Ichiji, Norihiro Sugita, Natsuko Kobayashi, Saya Kikuchi, Yasuto Kunii, Keiko Murakami, Mami Ishikuro, Taku Obara, Tomohiro Nakamura, Fuji Nagami, Takako Takai, Soichi Ogishima, Junichi Sugawara, Tetsuro Hoshiai, Masatoshi Saito, Gen Tamiya, Nobuo Fuse, Shinichi Kuriyama, Masayuki Yamamoto, Nobuo Yaegashi, Noriyasu Homma, Hiroaki Tomita

    Frontiers in psychiatry　12　799029-799029　2021

    DOI： 10.3389/fpsyt.2021.799029 　

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    In this study, the extent to which different emotions of pregnant women can be predicted based on heart rate-relevant information as indicators of autonomic nervous system functioning was explored using various machine learning algorithms. Nine heart rate-relevant autonomic system indicators, including the coefficient of variation R-R interval (CVRR), standard deviation of all NN intervals (SDNN), and square root of the mean squared differences of successive NN intervals (RMSSD), were measured using a heart rate monitor (MyBeat) and four different emotions including "happy," as a positive emotion and "anxiety," "sad," "frustrated," as negative emotions were self-recorded on a smartphone application, during 1 week starting from 23rd to 32nd weeks of pregnancy from 85 pregnant women. The k-nearest neighbor (k-NN), support vector machine (SVM), logistic regression (LR), random forest (RF), naïve bayes (NB), decision tree (DT), gradient boosting trees (GBT), stochastic gradient descent (SGD), extreme gradient boosting (XGBoost), and artificial neural network (ANN) machine learning methods were applied to predict the four different emotions based on the heart rate-relevant information. To predict four different emotions, RF also showed a modest area under the receiver operating characteristic curve (AUC-ROC) of 0.70. CVRR, RMSSD, SDNN, high frequency (HF), and low frequency (LF) mostly contributed to the predictions. GBT displayed the second highest AUC (0.69). Comprehensive analyses revealed the benefits of the prediction accuracy of the RF and GBT methods and were beneficial to establish models to predict emotions based on autonomic nervous system indicators. The results implicated SDNN, RMSSD, CVRR, LF, and HF as important parameters for the predictions.

  105. 東北メディカル・メガバンク計画地域住民コホート 特定健診共同参加型対象者の基礎特性とがん罹患の関連

    寳澤 篤, 小原 拓, 中村 智洋, 板橋 芙美, 小暮 真奈, 成田 暁, 土屋 菜歩, 平田 匠, 中谷 直樹, 菅原 準一, 栗山 進一, 布施 昇男, 辻 一郎, 呉 繁夫

    Journal of Epidemiology　31　(Suppl.)　116-116　2021/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  106. 東北メディカル・メガバンク計画地域住民コホート 特定健診共同参加型対象者の基礎特性とがん罹患の関連

    寳澤 篤, 小原 拓, 中村 智洋, 板橋 芙美, 小暮 真奈, 成田 暁, 土屋 菜歩, 平田 匠, 中谷 直樹, 菅原 準一, 栗山 進一, 布施 昇男, 辻 一郎, 呉 繁夫

    Journal of Epidemiology　31　(Suppl.)　116-116　2021/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  107. Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2). International-journal

    Hideki Tokunaga, Keita Iida, Atsushi Hozawa, Soichi Ogishima, Yoh Watanabe, Shogo Shigeta, Muneaki Shimada, Yumi Yamaguchi-Kabata, Shu Tadaka, Fumiki Katsuoka, Shin Ito, Kazuki Kumada, Yohei Hamanaka, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Yaegashi, Jun Yasuda

    PloS one　16　(1)　e0236907　2021

    DOI： 10.1371/journal.pone.0236907 　

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    Identification of the population frequencies of definitely pathogenic germline variants in two major hereditary breast and ovarian cancer syndrome (HBOC) genes, BRCA1/2, is essential to estimate the number of HBOC patients. In addition, the identification of moderately penetrant HBOC gene variants that contribute to increasing the risk of breast and ovarian cancers in a population is critical to establish personalized health care. A prospective cohort subjected to genome analysis can provide both sets of information. Computational scoring and prospective cohort studies may help to identify such likely pathogenic variants in the general population. We annotated the variants in the BRCA1 and BRCA2 genes from a dataset of 3,552 whole-genome sequences obtained from members of a prospective cohorts with genome data in the Tohoku Medical Megabank Project (TMM) with InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAFs) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar were used for filtration criteria. Familial predispositions to cancers among the 35,000 TMM genome cohort participants were analyzed to verify the identified pathogenicity. Seven potentially pathogenic variants were newly identified. The sisters of carriers of these moderately deleterious variants and definite P and LP variants among members of the TMM prospective cohort showed a statistically significant preponderance for cancer onset, from the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potentially pathogenic variants in BRCA genes in the Japanese population. These results should help to follow up the carriers of variants of uncertain significance in the HBOC genes in the longitudinal prospective cohort study.

  108. Combining MRI and genetic data in the Tohoku Medical Megabank Organization cohort study for innovative Alzheimer’s disease research

    Makiko Taira, Nobuo Fuse, Shunji Mugikura, Kengo Kinoshita, Masayuki Yamamoto

    Alzheimer's &amp; Dementia　16　(S10)　2020/12

    Publisher: Wiley

    DOI： 10.1002/alz.045688 　

    ISSN： 1552-5260

    eISSN： 1552-5279

  109. Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity. International-journal

    Hiroshi Komatsu, Hikaru Takeuchi, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Kunio Iizuka, Yuji Takano, Yoshihisa Kakuto, Shunichi Funakoshi, Takashi Ono, Junko Ito, Yasuto Kunii, Mizuki Hino, Atsuko Nagaoka, Yasushi Iwasaki, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Hirotsugu Azechi, Noriko Kudo, Ryota Hashimoto, Hirooki Yabe, Mari Yoshida, Yuko Saito, Akiyoshi Kakita, Nobuo Fuse, Ryuta Kawashima, Yasuyuki Taki, Hiroaki Tomita

    Schizophrenia bulletin　46　(6)　1619-1628　2020/12/01

    DOI： 10.1093/schbul/sbaa049 　

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    Previous studies have indicated associations between several OLIG2 gene single-nucleotide polymorphisms (SNPs) and susceptibility to schizophrenia among Caucasians. Consistent with these findings, postmortem brain and diffusion tensor imaging studies have indicated that the schizophrenia-risk-associated allele (A) in the OLIG2 SNP rs1059004 predicts lower OLIG2 gene expression in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients and reduced white matter (WM) integrity of the corona radiata in normal brains among Caucasians. In an effort to replicate the association between this variant and WM integrity among healthy Japanese, we found that the number of A alleles was positively correlated with WM integrity in some fiber tracts, including the right posterior limb of the internal capsule, and with mean blood flow in a widespread area, including the inferior frontal operculum, orbital area, and triangular gyrus. Because the A allele affected WM integrity in opposite directions in Japanese and Caucasians, we investigated a possible association between the OLIG2 gene SNPs and the expression level of OLIG2 transcripts in postmortem DLPFCs. We evaluated rs1059004 and additional SNPs in the 5' upstream and 3' downstream regions of rs1059004 to cover the broader region of the OLIG2 gene. The 2 SNPs (rs1059004 and rs9653711) had opposite effects on OLIG2 gene expression in the DLPFC in Japanese and Caucasians. These findings suggest ethnicity-dependent opposite effects of OLIG2 gene SNPs on WM integrity and OLIG2 gene expression in the brain, which may partially explain the failures in replicating associations between genetic variants and psychiatric phenotypes among ethnicities.

  110. Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population. International-journal

    Seizo Koshiba, Ikuko N Motoike, Daisuke Saigusa, Jin Inoue, Yuichi Aoki, Shu Tadaka, Matsuyuki Shirota, Fumiki Katsuoka, Gen Tamiya, Naoko Minegishi, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto

    Communications biology　3　(1)　662-662　2020/11/11

    DOI： 10.1038/s42003-020-01383-5 　

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    We performed a metabolome genome-wide association study for the Japanese population in the prospective cohort study of Tohoku Medical Megabank. By combining whole-genome sequencing and nontarget metabolome analyses, we identified a large number of novel associations between genetic variants and plasma metabolites. Of the identified metabolite-associated genes, approximately half have already been shown to be involved in various diseases. We identified metabolite-associated genes involved in the metabolism of xenobiotics, some of which are from intestinal microorganisms, indicating that the identified genetic variants also markedly influence the interaction between the host and symbiotic bacteria. We also identified five associations that appeared to be female-specific. A number of rare variants that influence metabolite levels were also found, and combinations of common and rare variants influenced the metabolite levels more profoundly. These results support our contention that metabolic phenotyping provides important insights into how genetic and environmental factors provoke human diseases.

  111. 東北メディカル・メガバンク計画(宮城)における頸動脈エコーについて

    寳澤 篤, 土屋 菜歩, 中村 智洋, 宇留野 晃, 栗山 進一, 菅原 準一, 呉 繁夫, 布施 昇男, 山本 雅之

    超音波医学　47　(Suppl.)　S532-S532　2020/11

    Publisher: (公社)日本超音波医学会

    ISSN： 1346-1176

    eISSN： 1881-9311

  112. Maternal Baseline Characteristics and Perinatal Outcomes: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

    Junichi Sugawara, Mami Ishikuro, Taku Obara, Tomomi Onuma, Keiko Murakami, Masahiro Kikuya, Fumihiko Ueno, Aoi Noda, Satoshi Mizuno, Tomoko Kobayashi, Yohei Hamanaka, Kichiya Suzuki, Eiichi Kodama, Naho Tsuchiya, Akira Uruno, Yoichi Suzuki, Osamu Tanabe, Hideyasu Kiyomoto, Akito Tsuboi, Atsushi Shimizu, Seizo Koshiba, Naoko Minegishi, Soichi Ogishima, Gen Tamiya, Hirohito Metoki, Atsushi Hozawa, Nobuo Fuse, Kengo Kinoshita, Shigeo Kure, Nobuo Yaegashi, Shinichi Kuriyama, Masayuki Yamamoto

    Journal of epidemiology　32　(2)　69-79　2020/10/10

    DOI： 10.2188/jea.JE20200338 　

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    BACKGROUND: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study was launched in 2013 to evaluate the complex interactions of genetic and environmental factors in multifactorial diseases. The present study describes the maternal baseline profile and perinatal data of participating mothers and infants. METHODS: Expectant mothers living in Miyagi prefecture were recruited from obstetric facilities or affiliated centers between 2013 and 2017. Three sets of self-administered questionnaires were collected, and the medical records were reviewed to obtain precise information about each antenatal visit and each delivery. Biospecimens, including blood, urine, umbilical cord blood, and breast milk, were collected for the study biobank. The baseline maternal sociodemographic characteristics, results of screening tests, and obstetric outcomes were analyzed according to the maternal age group. RESULTS: A total of 23 406 pregnancies involving 23 730 fetuses resulted in 23 143 live births. Younger maternal participants had a tendency toward a higher incidence of threatened abortion and threatened premature labor, while older age groups exhibited a significantly higher rate of low lying placenta, placenta previa, gestational diabetes and hypertensive disorders of pregnancy. CONCLUSIONS: The present study clearly shows the distribution of maternal baseline characteristics and the range of perinatal outcomes according to maternal age group. This cohort study can provide strategic information for creating breakthroughs in the pathophysiology of perinatal, developmental, and noncommunicable diseases by collaborative data visiting or sharing.

  113. EAAT1 variants associated with glaucoma. International-journal

    Michiko Yanagisawa, Kazuhiko Namekata, Tomomi Aida, Sayaka Katou, Takuya Takeda, Takayuki Harada, Nobuo Fuse, The Glaucoma Gene Research Group, Kohichi Tanaka

    Biochemical and biophysical research communications　529　(4)　943-949　2020/09/03

    DOI： 10.1016/j.bbrc.2020.06.099 　

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    Glaucoma is one of the leading causes of blindness characterized by progressive loss of retinal ganglion cells (RGCs) and their axons. We reported that glutamate/aspartate transporter (GLAST) knockout mice showed progressive RGC loss and optic nerve degeneration that are similar to glaucoma. To explore the possibility that rare variants in the EAAT1 gene (the human homolog of GLAST) cause susceptibility to glaucoma, we performed targeted sequencing of EAAT1 in 440 patients with glaucoma and 450 control subjects. We identified 8 rare variants in 20 out of 440 patients, including 4 synonymous and 4 missense variants located at protein coding regions. One of these rare variants (rs117295512) showed significant association with the risk of glaucoma (OR = 10.44, P = 0.005). Furthermore, the allele frequency for loss-of-function EAAT1 variants, pAla169Gly and pAla329Thr, was 5.5 folds higher in the glaucoma (1.1%) compared with the control cohort (0.2%). These findings suggest that these rare variants may contribute to the pathogenesis of glaucoma and that loss-of-function variants in EAAT1 are present in a small number of patients with glaucoma.

  114. COPD 疫学・病因・病態 出生体重と20代成人の%FEV1は相関する 東北メディカル・メガバンク機構住民健康調査に基づく呼吸機能影響因子の探索

    大江 崇, 山田 充啓, 杉浦 久敏, 布施 昇男, 寳澤 篤, 中村 智洋, 山本 雅之, 一ノ瀬 正和

    日本呼吸器学会誌　9　(増刊)　125-125　2020/08

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  115. Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes in a 3,552 Japanese whole-genome sequence dataset (3.5KJPNv2) Peer-reviewed

    Hideki Tokunaga, Keita Iida, Atsushi Hozawa, Soichi Ogishima, Yoh Watanabe, Shogo Shigeta, Muneaki Shimada, Yumi Yamaguchi-Kabata, Shu Tadaka, Fumiki Katsuoka, Shin Ito, Kazuki Kumada, Yohei Hamanaka, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Yaegashi, Jun Yasuda

    2020/07/17

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2020.07.17.208454 　

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    <title>Abstract</title>Identification of pathogenic germline variants yet no clinical evidence in <italic>BRCA</italic> genes has become important in patient care of hereditary breast and ovarian cancer syndrome (HBOC). Computational scoring and prospective cohort studies may help to identify such pathogenic variants. We annotated the variants in the <italic>BRCA1</italic> and <italic>BRCA2</italic> genes from a dataset of 3,552 whole-genome sequences obtained from members of the genome cohorts by Tohoku Medical Megabank Project (TMM) with the InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAF) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar are used for filtration criteria. Familial predispositions in cancers among the 35,000 TMM genome cohort participants are analyzed to verify the pathogenicity. Seven potentially pathogenic variants were newly identified. Carriers of these potential pathogenic variants and definite P and LP variants among participants of the TMM prospective cohort show a statistically significant preponderance in cancer onset in sisters in the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potential pathogenic variants in <italic>BRCA</italic> genes for Japanese population. These results will be helpful to follow up the carriers of variants of uncertain significance in the HBOC genes.

  116. Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer. International-journal

    Yingsong Lin, Masahiro Nakatochi, Yasuyuki Hosono, Hidemi Ito, Yoichiro Kamatani, Akihito Inoko, Hiromi Sakamoto, Fumie Kinoshita, Yumiko Kobayashi, Hiroshi Ishii, Masato Ozaka, Takashi Sasaki, Masato Matsuyama, Naoki Sasahira, Manabu Morimoto, Satoshi Kobayashi, Taito Fukushima, Makoto Ueno, Shinichi Ohkawa, Naoto Egawa, Sawako Kuruma, Mitsuru Mori, Haruhisa Nakao, Yasushi Adachi, Masumi Okuda, Takako Osaki, Shigeru Kamiya, Chaochen Wang, Kazuo Hara, Yasuhiro Shimizu, Tatsuo Miyamoto, Yuko Hayashi, Hiromichi Ebi, Tomohiro Kohmoto, Issei Imoto, Yumiko Kasugai, Yoshinori Murakami, Masato Akiyama, Kazuyoshi Ishigaki, Koichi Matsuda, Makoto Hirata, Kazuaki Shimada, Takuji Okusaka, Takahisa Kawaguchi, Meiko Takahashi, Yoshiyuki Watanabe, Kiyonori Kuriki, Aya Kadota, Rieko Okada, Haruo Mikami, Toshiro Takezaki, Sadao Suzuki, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Atsushi Goto, Kengo Kinoshita, Nobuo Fuse, Fumiki Katsuoka, Atsushi Shimizu, Satoshi S Nishizuka, Kozo Tanno, Ken Suzuki, Yukinori Okada, Momoko Horikoshi, Toshimasa Yamauchi, Takashi Kadowaki, Herbert Yu, Jun Zhong, Laufey T Amundadottir, Yuichiro Doki, Hideshi Ishii, Hidetoshi Eguchi, David Bogumil, Christopher A Haiman, Loic Le Marchand, Masaki Mori, Harvey Risch, Veronica W Setiawan, Shoichiro Tsugane, Kenji Wakai, Teruhiko Yoshida, Fumihiko Matsuda, Michiaki Kubo, Shogo Kikuchi, Keitaro Matsuo

    Nature communications　11　(1)　3175-3175　2020/06/24

    DOI： 10.1038/s41467-020-16711-w 　

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    Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10-8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

  117. ゲノムコホート調査におけるゲノム薬理学(PGx)遺伝情報返却(回付)のパイロット研究

    濱中 洋平, 大根田 絹子, 布施 昇男, 川目 裕, 長神 風二, 平塚 真弘, 宇留野 晃, 櫻井 美佳, 平良 摩紀子, 鈴木 吉也, 鈴木 洋一, 山本 雅之

    日本遺伝カウンセリング学会誌　41　(2)　122-122　2020/06

    Publisher: (一社)日本遺伝カウンセリング学会

    ISSN： 1347-9628

  118. Design and Progress of Oral Health Examinations in the Tohoku Medical Megabank Project.

    Akito Tsuboi, Hiroyuki Matsui, Naru Shiraishi, Takahisa Murakami, Akihito Otsuki, Junko Kawashima, Tomomi Kiyama, Toru Tamahara, Maki Goto, Shihoko Koyama, Junichi Sugawara, Eiichi N Kodama, Hirohito Metoki, Atsushi Hozawa, Shinichi Kuriyama, Hiroaki Tomita, Masahiro Kikuya, Naoko Minegishi, Kichiya Suzuki, Seizo Koshiba, Gen Tamiya, Nobuo Fuse, Yuichi Aoki, Takako Takai-Igarashi, Soichi Ogishima, Tomohiro Nakamura, Mika Sakurai-Yageta, Fuji Nagami, Kengo Kinoshita, Shigeo Kure, Ritsuko Shimizu, Keiichi Sasaki, Masayuki Yamamoto

    The Tohoku journal of experimental medicine　251　(2)　97-115　2020/06

    DOI： 10.1620/tjem.251.97 　

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    In order to assess the long-term impact of the Great East Japan Earthquake on the oral health of disaster victims and to evaluate gene-environmental interactions in the development of major oral diseases and oral-systemic associations, the oral part of two large-scale genome cohort studies by the Tohoku Medical Megabank Organization (ToMMo), including the Community-based cohort (CommCohort) study and the Birth and Three-Generation cohort (BirThree) study, have been conducted. The study population comprised 32,185 subjects, including 16,886 participants in the CommCohort study and 15,299 participants in the BirThree cohort study, recruited from 2013 to 2017. The oral studies consist of a questionnaire regarding oral hygiene behavior, clinical examinations by dentists, and oral plaque and saliva sampling for microbiome analyses, which were carried out at seven community support centers in Miyagi prefecture. The median age of all participants was 55.0 years, and 66.1% of participants were women. Almost all participants reported that they brushed their teeth more than once a day. The median number of present teeth was 27.0, and the decayed, missing and filled tooth number was 16.0, with a significant difference according to age and sex. The median periodontal pocket and clinical attachment level was 2.48 mm and 4.00 mm, respectively. Periodontal parameters increased significantly according to age, except for the accumulation of dental calculus. The oral part of these extensive cross-sectional studies provides a unique and important platform for future studies on oral health and diseases that elicit through interactions with systemic diseases, lifestyles, life events and genetic backgrounds, and contributes to researches clarifying the long-term effects of disasters on oral health.

  119. コホート調査参加者に対するゲノム薬理学(PGx)遺伝情報の返却(回付) 個別化予防・医療の確立を目指して

    大根田 絹子, 布施 昇男, 川目 裕, 長神 風二, 平塚 真弘, 櫻井 美佳, 濱中 洋平, 鈴木 吉也, 鈴木 洋一, 山本 雅之

    日本薬学会年会要旨集　140年会　27K-pm08　2020/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  120. Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective. International-journal Peer-reviewed

    Shinichi Kuriyama, Hirohito Metoki, Masahiro Kikuya, Taku Obara, Mami Ishikuro, Chizuru Yamanaka, Masato Nagai, Hiroko Matsubara, Tomoko Kobayashi, Junichi Sugawara, Gen Tamiya, Atsushi Hozawa, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Akira Narita, Mana Kogure, Takumi Hirata, Ichiro Tsuji, Fuji Nagami, Nobuo Fuse, Tomohiko Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Yoichi Suzuki, Noriko Osumi, Keiko Nakayama, Kiyoshi Ito, Shinichi Egawa, Koichi Chida, Eiichi Kodama, Hideyasu Kiyomoto, Tadashi Ishii, Akito Tsuboi, Hiroaki Tomita, Yasuyuki Taki, Hiroshi Kawame, Kichiya Suzuki, Naoto Ishii, Soichi Ogishima, Satoshi Mizuno, Takako Takai-Igarashi, Naoko Minegishi, Jun Yasuda, Kazuhiko Igarashi, Ritsuko Shimizu, Masao Nagasaki, Osamu Tanabe, Seizo Koshiba, Hiroaki Hashizume, Hozumi Motohashi, Teiji Tominaga, Sadayoshi Ito, Kozo Tanno, Kiyomi Sakata, Atsushi Shimizu, Jiro Hitomi, Makoto Sasaki, Kengo Kinoshita, Hiroshi Tanaka, Tadao Kobayashi, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto

    International journal of epidemiology　49　(1)　18-19　2020/02/01

    DOI： 10.1093/ije/dyz169 　

    ISSN： 0300-5771

  121. Identification of a novel uterine leiomyoma GWAS locus in a Japanese population. International-journal

    Kensuke Sakai, Chizu Tanikawa, Akira Hirasawa, Tatsuyuki Chiyoda, Wataru Yamagami, Fumio Kataoka, Nobuyuki Susumu, Chikashi Terao, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Michiaki Kubo, Nobuo Fuse, Takako Takai-Igarashi, Atsushi Shimizu, Akimune Fukushima, Aya Kadota, Kokichi Arisawa, Hiroaki Ikezaki, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Daisuke Aoki, Koichi Matsuda

    Scientific reports　10　(1)　1197-1197　2020/01/27

    DOI： 10.1038/s41598-020-58066-8 　

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    Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10-25 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.

  122. Oral Microbiome Analysis in Prospective Genome Cohort Studies of the Tohoku Medical Megabank Project. International-journal

    Sakae Saito, Yuichi Aoki, Toru Tamahara, Maki Goto, Hiroyuki Matsui, Junko Kawashima, Inaho Danjoh, Atsushi Hozawa, Shinichi Kuriyama, Yoichi Suzuki, Nobuo Fuse, Shigeo Kure, Riu Yamashita, Osamu Tanabe, Naoko Minegishi, Kengo Kinoshita, Akito Tsuboi, Ritsuko Shimizu, Masayuki Yamamoto

    Frontiers in cellular and infection microbiology　10　604596-604596　2020

    DOI： 10.3389/fcimb.2020.604596 　

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    A baseline oral microbiome study of the Tohoku Medical Megabank Organization (TMM) was planned to characterize the profile of the oral microbiome in the Japanese population. The study also aimed to clarify risk factors for multifactorial diseases by integrated analysis of the oral microbiome and host genome/omics information. From 2013 to 2016, we collected three types of oral biospecimens, saliva, supragingival plaque, and tongue swab, from a total of 25,101 participants who had a dental examination in TMM. In this study, we used two independent cohorts; the Community-Based Cohort and Birth and Three-Generation Cohort as discovery and validation cohorts, respectively, and we selected participants examined by a single dentist. We found through the 16S ribosomal RNA gene sequencing analysis of 834 participants of the Community-Based Cohort Study that there are differences in the microbial composition and community structure between saliva and plaque. The species diversities in both saliva and plaque were increased in correlation with the severity of periodontal disease. These results were nicely reproduced in the analysis of 455 participants of the Birth and Three-Generation Cohort Study. In addition, strong positive and negative associations of microbial taxa in both plaque and saliva with periodontitis-associated biofilm formation were detected by co-occurrence network analysis. The classes Actinobacteria and Bacilli, including oral health-associated bacterial species, showed a positive correlation in saliva. These results revealed differences in microbial composition and community structure between saliva and plaque and a correlation between microbial species and the severity of periodontal disease. We expect that the large database of the oral microbiome in the TMM biobank will help in the discovery of novel targets for the treatment and prevention of oral diseases, as well as for the discovery of therapeutic and/or preventive targets of systemic diseases.

  123. TMM計画地域住民コホート調査(宮城)調査票項目と総死亡の関連

    寳澤 篤, 土屋 菜歩, 平田 匠, 成田 暁, 小暮 真奈, 中村 智洋, 小原 拓, 中谷 直樹, 丹野 高三, 菅原 準一, 栗山 進一, 辻 一郎, 呉 繁夫, 布施 昇男, 山本 雅之

    日本公衆衛生学会総会抄録集　78回　212-212　2019/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  124. TMM計画地域住民コホート調査(宮城)調査票項目と総死亡の関連 Peer-reviewed

    寳澤 篤, 土屋 菜歩, 平田 匠, 成田 暁, 小暮 真奈, 中村 智洋, 小原 拓, 中谷 直樹, 丹野 高三, 菅原 準一, 栗山 進一, 辻 一郎, 呉 繁夫, 布施 昇男, 山本 雅之

    日本公衆衛生学会総会抄録集　78回　212-212　2019/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  125. Establishment of Integrated Biobank for Precision Medicine and Personalized Healthcare: The Tohoku Medical Megabank Project. Peer-reviewed

    Nobuo Fuse, Mika Sakurai-Yageta, Fumiki Katsuoka, Inaho Danjoh, Ritsuko Shimizu, Gen Tamiya, Fuji Nagami, Hiroshi Kawame, Shinichi Higuchi, Kengo Kinoshita, Shigeo Kure, Masayuki Yamamoto

    JMA journal　2　(2)　113-122　2019/09/04

    DOI： 10.31662/jmaj.2019-0014 　

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    The Tohoku Medical Megabank (TMM) project was established to provide creative reconstruction of the Tohoku area that suffered from a huge earthquake and ensuing tsunami (the Great East Japan Earthquake, GEJE). TMM aims to establish two large-scale genome cohorts and an integrated biobank managing biospecimen and related information. It supports community medicine by establishing next-generation medical systems through a combination of the prospective genome cohort studies with a total of 150,000 participants and genomic medicine. The strategies for genome analyses in TMM are to develop an elaborate genome reference panel by means of high-fidelity Japanese whole-genome sequence, to design custom single nucleotide polymorphism (SNP) arrays based on the reference panel, and to obtain genotype data for all the TMM cohort participants subsequently. Disease-associated genomic information and omics data, including metabolomics and microbiome analysis, provide an essential platform for precision medicine and personalized healthcare (PHC). Ethical, legal, and social issues (ELSI) and education are important for implementing genomic medicine. The major considerations of ELSI regarding each participant of the cohort studies are the respect for the autonomy and the protection of privacies. Moreover, developing and provide human resources not only for the TMM project but also for the social implementation of precision medicine and PHC is required. We started a pilot study of the return of genomic results for familial hypercholesterolemia (FH) as a target disease. TMM aims to establish solid platforms that support precision medicine and PHC based on the genomic and omics information and environmental and lifestyle factors of the individuals, which is one of the most advanced medical care beyond the evidenced-based medicine in the near future.

  126. 遺伝教育は血縁者の健康管理のために自身の遺伝学的検査結果を共有する意識を強くする

    徳富 智明, 吉田 明子, 福島 明宗, 山本 佳世乃, 石垣 泰, 川目 裕, 布施 昇男, 長神 風二, 鈴木 吉也, 宇留野 晃, 櫻井 美佳, 沼田 早苗, 中山 文予, 山本 雅之, 佐々木 真理

    日本遺伝カウンセリング学会誌　40　(2)　76-76　2019/07

    Publisher: (一社)日本遺伝カウンセリング学会

    ISSN： 1347-9628

  127. 大規模ゲノムコホート調査におけるBRCA1/2遺伝子の病的バリアント保持者への遺伝情報回付に関する課題

    濱中 洋平, 石田 孝宣, 布施 昇男, 川目 裕, 山口 由美, 安田 純, 多田 寛, 宮下 穣, 原田 成美, 佐藤 章子, 青木 洋子, 長神 風二, 八重樫 伸生, 木下 賢吾, 呉 繁夫, 山本 雅之

    日本乳癌学会総会プログラム抄録集　27回　332-332　2019/07

    Publisher: (一社)日本乳癌学会

  128. A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy. International-journal Peer-reviewed

    Konstantinos Nikopoulos, Katarina Cisarova, Mathieu Quinodoz, Hanna Koskiniemi-Kuendig, Noriko Miyake, Pietro Farinelli, Atta Ur Rehman, Muhammad Imran Khan, Andrea Prunotto, Masato Akiyama, Yoichiro Kamatani, Chikashi Terao, Fuyuki Miya, Yasuhiro Ikeda, Shinji Ueno, Nobuo Fuse, Akira Murakami, Yuko Wada, Hiroko Terasaki, Koh-Hei Sonoda, Tatsuro Ishibashi, Michiaki Kubo, Frans P M Cremers, Zoltán Kutalik, Naomichi Matsumoto, Koji M Nishiguchi, Toru Nakazawa, Carlo Rivolta

    Nature communications　10　(1)　2884-2884　2019/06/28

    DOI： 10.1038/s41467-019-10746-4 　

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    Hereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e., a 3.5-fold enrichment; p-value = 9.2 × 10-5). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation in trans with the Alu insertion, but might also associate with disease in combination with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance.

  129. Construction of full-length Japanese reference panel of class I HLA genes with single-molecule, real-time sequencing Peer-reviewed

    Takahiro Mimori, Jun Yasuda, Yoko Kuroki, Tomoko F. Shibata, Fumiki Katsuoka, Sakae Saito, Naoki Nariai, Akira Ono, Naomi Nakai-Inagaki, Kazuharu Misawa, Keiko Tateno, Yosuke Kawai, Nobuo Fuse, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Kichiya Suzuki, Kengo Kinoshita, Masao Nagasaki, Masayuki Yamamoto

    The Pharmacogenomics Journal　19　(2)　136-146　2019/04/19

    Publisher: Springer Nature

    DOI： 10.1038/s41397-017-0010-4 　

    ISSN： 1470-269X

  130. Identification of genetic alterations in extramammary Paget disease using whole exome analysis. International-journal Peer-reviewed

    Yukiko Kiniwa, Jun Yasuda, Sakae Saito, Rumiko Saito, Ikuko N Motoike, Inaho Danjoh, Kengo Kinoshita, Nobuo Fuse, Masayuki Yamamoto, Ryuhei Okuyama

    Journal of dermatological science　94　(1)　229-235　2019/04

    DOI： 10.1016/j.jdermsci.2019.03.006 　

    ISSN： 0923-1811

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    BACKGROUND: Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm, and the genomic alterations underlying its pathogenesis are unknown. OBJECTIVE: To identify tumor-specific genomic alterations in EMPD. METHODS: Exome analysis was performed in specimens from three EMPD patients, and target amplicon sequencing was done for genes frequently mutated in other adenocarcinomas. RESULTS: Exome analysis revealed recurrent somatic mutations in several genes, includingTP53, PIK3CA, and ERBB2. We identified additional candidate exons by searching the COSMIC database for exons that are frequently mutated in other adenocarcinomas. We obtained 19 exons in 12 genes as candidate exons, and performed target amplicon sequencing in samples obtained from EMPD patients. New somatic mutations in the TP53 gene were identified in six EMPD patients. Single nucleotide polymorphism analysis revealed multiple chromosomal alterations in three EMPD specimens, and two specimens exhibited amplification of chromosome 12p13 and losses of 3p21-24, 7q22 and 13q12-21. CONCLUSION: Our comprehensive genetic analysis identified novel genomic alterations, and will inform treatment options for EMPD.

  131. Estimating carrier frequencies of newborn screening disorders using a whole-genome reference panel of 3552 Japanese individuals. International-journal Peer-reviewed

    Yumi Yamaguchi-Kabata, Jun Yasuda, Akira Uruno, Kazuro Shimokawa, Seizo Koshiba, Yoichi Suzuki, Nobuo Fuse, Hiroshi Kawame, Shu Tadaka, Masao Nagasaki, Kaname Kojima, Fumiki Katsuoka, Kazuki Kumada, Osamu Tanabe, Gen Tamiya, Nobuo Yaegashi, Kengo Kinoshita, Masayuki Yamamoto, Shigeo Kure

    Human genetics　138　(4)　389-409　2019/04

    DOI： 10.1007/s00439-019-01998-7 　

    ISSN： 0340-6717

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    Incidence rates of Mendelian diseases vary among ethnic groups, and frequencies of variant types of causative genes also vary among human populations. In this study, we examined to what extent we can predict population frequencies of recessive disorders from genomic data, and explored better strategies for variant interpretation and classification. We used a whole-genome reference panel from 3552 general Japanese individuals constructed by the Tohoku Medical Megabank Organization (ToMMo). Focusing on 32 genes for 17 congenital metabolic disorders included in newborn screening (NBS) in Japan, we identified reported and predicted pathogenic variants through variant annotation, interpretation, and multiple ways of classifications. The estimated carrier frequencies were compared with those from the Japanese NBS data based on 1,949,987 newborns from a previous study. The estimated carrier frequency based on genomic data with a recent guideline of variant interpretation for the PAH gene, in which defects cause hyperphenylalaninemia (HPA) and phenylketonuria (PKU), provided a closer estimate to that by the observed incidence than the other methods. In contrast, the estimated carrier frequencies for SLC25A13, which causes citrin deficiency, were much higher compared with the incidence rate. The results varied greatly among the 11 NBS diseases with single responsible genes; the possible reasons for departures from the carrier frequencies by reported incidence rates were discussed. Of note, (1) the number of pathogenic variants increases by including additional lines of evidence, (2) common variants with mild effects also contribute to the actual frequency of patients, and (3) penetrance of each variant remains unclear.

  132. Maternity Log study: a longitudinal lifelog monitoring and multiomics analysis for the early prediction of complicated pregnancy. International-journal Peer-reviewed

    Junichi Sugawara, Daisuke Ochi, Riu Yamashita, Takafumi Yamauchi, Daisuke Saigusa, Maiko Wagata, Taku Obara, Mami Ishikuro, Yoshiki Tsunemoto, Yuki Harada, Tomoko Shibata, Takahiro Mimori, Junko Kawashima, Fumiki Katsuoka, Takako Igarashi-Takai, Soichi Ogishima, Hirohito Metoki, Hiroaki Hashizume, Nobuo Fuse, Naoko Minegishi, Seizo Koshiba, Osamu Tanabe, Shinichi Kuriyama, Kengo Kinoshita, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto, Satoshi Hiyama, Masao Nagasaki

    BMJ open　9　(2)　e025939　2019/02/19

    DOI： 10.1136/bmjopen-2018-025939 　

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    PURPOSE: A prospective cohort study for pregnant women, the Maternity Log study, was designed to construct a time-course high-resolution reference catalogue of bioinformatic data in pregnancy and explore the associations between genomic and environmental factors and the onset of pregnancy complications, such as hypertensive disorders of pregnancy, gestational diabetes mellitus and preterm labour, using continuous lifestyle monitoring combined with multiomics data on the genome, transcriptome, proteome, metabolome and microbiome. PARTICIPANTS: Pregnant women were recruited at the timing of first routine antenatal visits at Tohoku University Hospital, Sendai, Japan, between September 2015 and November 2016. Of the eligible women who were invited, 65.4% agreed to participate, and a total of 302 women were enrolled. The inclusion criteria were age ≥20 years and the ability to access the internet using a smartphone in the Japanese language. FINDINGS TO DATE: Study participants uploaded daily general health information including quality of sleep, condition of bowel movements and the presence of nausea, pain and uterine contractions. Participants also collected physiological data, such as body weight, blood pressure, heart rate and body temperature, using multiple home healthcare devices. The mean upload rate for each lifelog item was ranging from 67.4% (fetal movement) to 85.3% (physical activity), and the total number of data points was over 6 million. Biospecimens, including maternal plasma, serum, urine, saliva, dental plaque and cord blood, were collected for multiomics analysis. FUTURE PLANS: Lifelog and multiomics data will be used to construct a time-course high-resolution reference catalogue of pregnancy. The reference catalogue will allow us to discover relationships among multidimensional phenotypes and novel risk markers in pregnancy for the future personalised early prediction of pregnancy complications.

  133. Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare. International-journal Peer-reviewed

    Jun Yasuda, Kengo Kinoshita, Fumiki Katsuoka, Inaho Danjoh, Mika Sakurai-Yageta, Ikuko N Motoike, Yoko Kuroki, Sakae Saito, Kaname Kojima, Matsuyuki Shirota, Daisuke Saigusa, Akihito Otsuki, Junko Kawashima, Yumi Yamaguchi-Kabata, Shu Tadaka, Yuichi Aoki, Takahiro Mimori, Kazuki Kumada, Jin Inoue, Satoshi Makino, Miho Kuriki, Nobuo Fuse, Seizo Koshiba, Osamu Tanabe, Masao Nagasaki, Gen Tamiya, Ritsuko Shimizu, Takako Takai-Igarashi, Soichi Ogishima, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Akito Tsuboi, Hideyasu Kiyomoto, Tadashi Ishii, Hiroaki Tomita, Naoko Minegishi, Yoichi Suzuki, Kichiya Suzuki, Hiroshi Kawame, Hiroshi Tanaka, Yasuyuki Taki, Nobuo Yaegashi, Shigeo Kure, Fuji Nagami, Kenjiro Kosaki, Yoichi Sutoh, Tsuyoshi Hachiya, Atsushi Shimizu, Makoto Sasaki, Masayuki Yamamoto

    Journal of biochemistry　165　(2)　139-158　2019/02/01

    DOI： 10.1093/jb/mvy096 　

    ISSN： 0021-924X

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    Personalized healthcare (PHC) based on an individual's genetic make-up is one of the most advanced, yet feasible, forms of medical care. The Tohoku Medical Megabank (TMM) Project aims to combine population genomics, medical genetics and prospective cohort studies to develop a critical infrastructure for the establishment of PHC. To date, a TMM CommCohort (adult general population) and a TMM BirThree Cohort (birth+three-generation families) have conducted recruitments and baseline surveys. Genome analyses as part of the TMM Project will aid in the development of a high-fidelity whole-genome Japanese reference panel, in designing custom single-nucleotide polymorphism (SNP) arrays specific to Japanese, and in estimation of the biological significance of genetic variations through linked investigations of the cohorts. Whole-genome sequencing from >3,500 unrelated Japanese and establishment of a Japanese reference genome sequence from long-read data have been done. We next aim to obtain genotype data for all TMM cohort participants (>150,000) using our custom SNP arrays. These data will help identify disease-associated genomic signatures in the Japanese population, while genomic data from TMM BirThree Cohort participants will be used to improve the reference genome panel. Follow-up of the cohort participants will allow us to test the genetic markers and, consequently, contribute to the realization of PHC.

  134. 3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome. International-journal Peer-reviewed

    Shu Tadaka, Fumiki Katsuoka, Masao Ueki, Kaname Kojima, Satoshi Makino, Sakae Saito, Akihito Otsuki, Chinatsu Gocho, Mika Sakurai-Yageta, Inaho Danjoh, Ikuko N Motoike, Yumi Yamaguchi-Kabata, Matsuyuki Shirota, Seizo Koshiba, Masao Nagasaki, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Atsushi Shimizu, Jun Yasuda, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

    Human genome variation　6　28-28　2019

    DOI： 10.1038/s41439-019-0059-5 　

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    The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, it will be useful to construct population-level allele frequency panels with easy-to-use interfaces. In the Tohoku Medical Megabank Project, we sequenced nearly 4000 individuals from a Japanese population and constructed an allele frequency panel of 3552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first large-scale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.

  135. Construction of JRG (Japanese reference genome) with single-molecule real-time sequencing. International-journal Peer-reviewed

    Masao Nagasaki, Yoko Kuroki, Tomoko F Shibata, Fumiki Katsuoka, Takahiro Mimori, Yosuke Kawai, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Yoichi Suzuki, Hiroshi Kawame, Fuji Nagami, Takako Takai-Igarashi, Soichi Ogishima, Kaname Kojima, Kazuharu Misawa, Osamu Tanabe, Nobuo Fuse, Hiroshi Tanaka, Nobuo Yaegashi, Kengo Kinoshita, Shiego Kure, Jun Yasuda, Masayuki Yamamoto

    Human genome variation　6　27-27　2019

    DOI： 10.1038/s41439-019-0057-7 　

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    In recent genome analyses, population-specific reference panels have indicated important. However, reference panels based on short-read sequencing data do not sufficiently cover long insertions. Therefore, the nature of long insertions has not been well documented. Here, we assembled a Japanese genome using single-molecule real-time sequencing data and characterized insertions found in the assembled genome. We identified 3691 insertions ranging from 100 bps to ~10,000 bps in the assembled genome relative to the international reference sequence (GRCh38). To validate and characterize these insertions, we mapped short-reads from 1070 Japanese individuals and 728 individuals from eight other populations to insertions integrated into GRCh38. With this result, we constructed JRGv1 (Japanese Reference Genome version 1) by integrating the 903 verified insertions, totaling 1,086,173 bases, shared by at least two Japanese individuals into GRCh38. We also constructed decoyJRGv1 by concatenating 3559 verified insertions, totaling 2,536,870 bases, shared by at least two Japanese individuals or by six other assemblies. This assembly improved the alignment ratio by 0.4% on average. These results demonstrate the importance of refining the reference assembly and creating a population-specific reference genome. JRGv1 and decoyJRGv1 are available at the JRG website.

  136. Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21. International-journal Peer-reviewed

    Tanikawa C, Kamatani Y, Toyoshima O, Sakamoto H, Ito H, Takahashi A, Momozawa Y, Hirata M, Fuse N, Takai-Igarashi T, Shimizu A, Sasaki M, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Naito M, Hishida A, Wakai K, Furusyo N, Murakami Y, Nakamura Y, Imoto I, Inazawa J, Oze I, Sato N, Tanioka F, Sugimura H, Hirose H, Yoshida T, Matsuo K, Kubo M, Matsuda K

    Cancer science　109　(12)　4015-4024　2018/12

    DOI： 10.1111/cas.13815 　

    ISSN： 1347-9032

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    Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large-scale genome-wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P = 3.20 × 10-8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10-10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10-13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10-11 ), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.

  137. Regional genetic differences among Japanese populations and performance of genotype imputation using whole-genome reference panel of the Tohoku Medical Megabank Project. International-journal Peer-reviewed

    Jun Yasuda, Fumiki Katsuoka, Inaho Danjoh, Yosuke Kawai, Kaname Kojima, Masao Nagasaki, Sakae Saito, Yumi Yamaguchi-Kabata, Shu Tadaka, Ikuko N Motoike, Kazuki Kumada, Mika Sakurai-Yageta, Osamu Tanabe, Nobuo Fuse, Gen Tamiya, Koichiro Higasa, Fumihiko Matsuda, Nobufumi Yasuda, Motoki Iwasaki, Makoto Sasaki, Atsushi Shimizu, Kengo Kinoshita, Masayuki Yamamoto

    BMC genomics　19　(1)　551-551　2018/07/24

    DOI： 10.1186/s12864-018-4942-0 　

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    BACKGROUND: Genotype imputation from single-nucleotide polymorphism (SNP) genotype data using a haplotype reference panel consisting of thousands of unrelated individuals from populations of interest can help to identify strongly associated variants in genome-wide association studies. The Tohoku Medical Megabank (TMM) project was established to support the development of precision medicine, together with the whole-genome sequencing of 1070 human genomes from individuals in the Miyagi region (Northeast Japan) and the construction of the 1070 Japanese genome reference panel (1KJPN). Here, we investigated the performance of 1KJPN for genotype imputation of Japanese samples not included in the TMM project and compared it with other population reference panels. RESULTS: We found that the 1KJPN population was more similar to other Japanese populations, Nagahama (south-central Japan) and Aki (Shikoku Island), than to East Asian populations in the 1000 Genomes Project other than JPT, suggesting that the large-scale collection (more than 1000) of Japanese genomes from the Miyagi region covered many of the genetic variations of Japanese in mainland Japan. Moreover, 1KJPN outperformed the phase 3 reference panel of the 1000 Genomes Project (1KGPp3) for Japanese samples, and IKJPN showed similar imputation rates for the TMM and other Japanese samples for SNPs with minor allele frequencies (MAFs) higher than 1%. CONCLUSIONS: 1KJPN covered most of the variants found in the samples from areas of the Japanese mainland outside the Miyagi region, implying 1KJPN is representative of the Japanese population's genomes. 1KJPN and successive reference panels are useful genome reference panels for the mainland Japanese population. Importantly, the addition of whole genome sequences not included in the 1KJPN panel improved imputation efficiencies for SNPs with MAFs under 1% for samples from most regions of the Japanese archipelago.

  138. Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project. International-journal Peer-reviewed

    Seizo Koshiba, Ikuko Motoike, Daisuke Saigusa, Jin Inoue, Matsuyuki Shirota, Yasutake Katoh, Fumiki Katsuoka, Inaho Danjoh, Atsushi Hozawa, Shinichi Kuriyama, Naoko Minegishi, Masao Nagasaki, Takako Takai-Igarashi, Soichi Ogishima, Nobuo Fuse, Shigeo Kure, Gen Tamiya, Osamu Tanabe, Jun Yasuda, Kengo Kinoshita, Masayuki Yamamoto

    Genes to cells : devoted to molecular & cellular mechanisms　23　(6)　406-417　2018/06

    DOI： 10.1111/gtc.12588 　

    ISSN： 1356-9597

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    Population-based prospective cohort studies are indispensable for modern medical research as they provide important knowledge on the influences of many kinds of genetic and environmental factors on the cause of disease. Although traditional cohort studies are mainly conducted using questionnaires and physical examinations, modern cohort studies incorporate omics and genomic approaches to obtain comprehensive physical information, including genetic information. Here, we report the design and midterm results of multi-omics analysis on population-based prospective cohort studies from the Tohoku Medical Megabank (TMM) Project. We have incorporated genomic and metabolomic studies in the TMM cohort study as both metabolome and genome analyses are suitable for high-throughput analysis of large-scale cohort samples. Moreover, an association study between the metabolome and genome show that metabolites are an important intermediate phenotype connecting genetic and lifestyle factors to physical and pathologic phenotypes. We apply our metabolome and genome analyses to large-scale cohort samples in the following studies.

  139. Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma Peer-reviewed

    Yukihiro Shiga, Japan Glaucoma Society Omics Group (JGS-OG), Masato Akiyama, Koji M. Nishiguchi, Kota Sato, Nobuhiro Shimozawa, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Isao Oze, Haruo Mikami, Mariko Naito, Kenji Wakai, Munemitsu Yoshikawa, Masahiro Miyake, Kenji Yamashiro, Kenji Kashiwagi, Takeshi Iwata, Fumihiko Mabuchi, Mitsuko Takamoto, Mineo Ozaki, Kazuhide Kawase, Makoto Aihara, Makoto Araie, Tetsuya Yamamoto, Yoshiaki Kiuchi, Makoto Nakamura, Yasuhiro Ikeda, Koh-Hei Sonoda, Tatsuro Ishibashi, Koji Nitta, Aiko Iwase, Shiroaki Shirato, Yoshitaka Oka, Mamoru Satoh, Makoto Sasaki, Nobuo Fuse, Yoichi Suzuki, Ching-Yu Cheng, Chiea Chuen Khor, Mani Baskaran, Shamira Perera, Tin Aung, Eranga N. Vithana, Jessica N. Cooke Bailey, Jae H. Kang, Louis R. Pasquale, Jonathan L. Haines, Janey L. Wiggs, Kathryn P. Burdon, Puya Gharahkhani, Alex W. Hewitt, David A. Mackey, Stuart MacGregor, Jamie E. Craig, R. Rand Allingham, Micheal Hauser, Adeyinka Ashaye, Donald L. Budenz, Stephan Akafo, Susan E.I. Williams, Yoichiro Kamatani, Toru Nakazawa, Michiaki Kubo

    Human Molecular Genetics　27　(8)　1486-1496　2018/04/15

    Publisher: Oxford University Press

    DOI： 10.1093/hmg/ddy053 　

    ISSN： 1460-2083 0964-6906

  140. Impact of clinical factors and UGT1A9 and CYP2B6 genotype on inter-individual differences in propofol pharmacokinetics Peer-reviewed

    Akihiro Kanaya, Toshihiro Sato, Nobuo Fuse, Hiroaki Yamaguchi, Nariyasu Mano, Masanori Yamauchi

    Journal of Anesthesia　32　(2)　236-243　2018/04/01

    Publisher: Springer Tokyo

    DOI： 10.1007/s00540-018-2470-3 　

    ISSN： 1438-8359 0913-8668

  141. 東北メディカル・メガバンク地域住民コホート調査に基づく、日本人呼気一酸化窒素濃度の分布と影響因子の解析(中間報告) Peer-reviewed

    山田 充啓, 杉浦 久敏, 布施 昇男, 寳澤 篤, 高井 貴子, 土屋 奈歩, 光根 歩, 栗山 進一, 山本 雅之, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　213-213　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  142. Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals. International-journal Peer-reviewed

    Yumi Yamaguchi-Kabata, Jun Yasuda, Osamu Tanabe, Yoichi Suzuki, Hiroshi Kawame, Nobuo Fuse, Masao Nagasaki, Yosuke Kawai, Kaname Kojima, Fumiki Katsuoka, Sakae Saito, Inaho Danjoh, Ikuko N Motoike, Riu Yamashita, Seizo Koshiba, Daisuke Saigusa, Gen Tamiya, Shigeo Kure, Nobuo Yaegashi, Yoshio Kawaguchi, Fuji Nagami, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Atsushi Hozawa, Soichi Ogishima, Hideyasu Kiyomoto, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto

    Journal of human genetics　63　(2)　213-230　2018/02

    DOI： 10.1038/s10038-017-0347-1 　

    ISSN： 1434-5161

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    Clarifying allele frequencies of disease-related genetic variants in a population is important in genomic medicine; however, such data is not yet available for the Japanese population. To estimate frequencies of actionable pathogenic variants in the Japanese population, we examined the reported pathological variants in genes recommended by the American College of Medical Genetics and Genomics (ACMG) in our reference panel of genomic variations, 2KJPN, which was created by whole-genome sequencing of 2049 individuals of the resident cohort of the Tohoku Medical Megabank Project. We searched for pathogenic variants in 2KJPN for 57 autosomal ACMG-recommended genes responsible for 26 diseases and then examined their frequencies. By referring to public databases of pathogenic variations, we identified 143 reported pathogenic variants in 2KJPN for the 57 ACMG recommended genes based on a classification system. At the individual level, 21% of the individuals were found to have at least one reported pathogenic allele. We then conducted a literature survey to review the variants and to check for evidence of pathogenicity. Our results suggest that a substantial number of people have reported pathogenic alleles for the ACMG genes, and reviewing variants is indispensable for constructing the information infrastructure of genomic medicine for the Japanese population.

  143. A GWAS identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21. Peer-reviewed

    Tanikawa C, Kamatani Y, Toyoshima O, Sakamoto H, Ito H, Takahashi A, Momozawa Y, Hirata M, Fuse N, Takai-Igarashi T, Shimizu A, Sasaki M, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Naito M, Hishida A, Wakai K, Furusyo N, Murakami Y, Nakamura Y, Imoto I, Inazawa J, Oze I, Sato N, Tanioka F, Sugimura H, Hirose H, Yoshida T, Matsuo K, Michiaki K, Matsuda K

    Cancer Sci.　2018

  144. Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1. International-journal Peer-reviewed

    Varalee Yodsurang, Yaqi Tang, Yukie Takahashi, Chizu Tanikawa, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Nobuo Fuse, Junichi Sugawara, Atsushi Shimizu, Akimune Fukushima, Asahi Hishida, Norihiro Furusyo, Mariko Naito, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Makoto Hirata, Yoshinori Murakami, Michiaki Kubo, Koichi Matsuda

    PloS one　13　(12)　e0209096　2018

    DOI： 10.1371/journal.pone.0209096 　

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    Genome-wide association studies (GWAS) have identified greater than 30 variants associated with ovarian cancer, but most of these variants were investigated in European populations. Here, we integrated GWAS and subsequent functional analyses to identify the genetic variants with potential regulatory effects. We conducted GWAS for ovarian cancer using 681 Japanese cases and 17,492 controls and found that rs137672 on 22q13.1 exhibited a strong association with a P-value of 1.05 × 10(-7) and an odds ratio of 0.573 with a 95% confidence interval of 0.466-0.703. In addition, three previously reported SNPs, i.e., rs10088218, rs9870207 and rs1400482, were validated in the Japanese population (P < 0.05) with the same risk allele as noted in previous studies. Functional studies including regulatory feature analysis and electrophoretic mobility shift assay (EMSA) revealed two regulatory SNPs in 22q13.1, rs2072872 and rs6509, that affect the binding affinity to some nuclear proteins in ovarian cancer cells. The plausible regulatory proteins whose motifs could be affected by the allele changes of these two SNPs were also proposed. Moreover, the protective G allele of rs6509 was associated with a decreased SYNGR1 expression level in normal ovarian tissues. Our findings elucidated the regulatory variants in 22q13.1 that are associated with ovarian cancer risk.

  145. Genetic analysis of Japanese primary open-angle glaucoma patients and clinical characterization of risk alleles near CDKN2B-AS1, SIX6 and GAS7 Peer-reviewed

    Yukihiro Shiga, Japan Glaucoma Society Omics Group (JGS-OG), Koji M. Nishiguchi, Yosuke Kawai, Kaname Kojima, Kota Sato, Kosuke Fujita, Mai Takahashi, Kazuko Omodaka, Makoto Araie, Kenji Kashiwagi, Makoto Aihara, Takeshi Iwata, Fumihiko Mabuchi, Mitsuko Takamoto, Mineo Ozaki, Kazuhide Kawase, Nobuo Fuse, Masayuki Yamamoto, Jun Yasuda, Masao Nagasaki, Toru Nakazawa

    PLoS ONE　12　(12)　e0186678　2017/12/01

    Publisher: Public Library of Science

    DOI： 10.1371/journal.pone.0186678 　

    ISSN： 1932-6203

  146. 住民コホート研究における個人への遺伝情報回付(返却) 東北メディカル・メガバンク計画の試み

    川目 裕, 福島 明宗, 長神 風二, 鈴木 洋一, 川口 悦生, 布施 昇男, 徳富 智明, 山本 佳世乃, 沼田 早苗, 小林 朋子, 相澤 弥生, 佐々木 真理, 山本 雅之

    日本遺伝カウンセリング学会誌　38　(2)　95-95　2017/05

    Publisher: 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  147. ゲノムコホート研究における個人への遺伝情報の結果返却に関する遺伝カウンセリング記録の運用についての取り組みと今後の課題

    相澤 弥生, 高井 貴子, 沼田 早苗, 山本 佳世乃, 徳富 智明, 福島 明宗, 小林 朋子, 長神 風二, 鈴木 洋一, 川口 悦生, 布施 昇男, 川目 裕, 佐々木 真理, 山本 雅之

    日本遺伝カウンセリング学会誌　38　(2)　95-95　2017/05

    Publisher: 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  148. A Histologic Categorization of Aqueous Outflow Routes in Familial Open-Angle Glaucoma and Associations With Mutations in the MYOC Gene in Japanese Patients Peer-reviewed

    Teruhiko Hamanaka, Masae Kimura, Tetsuro Sakurai, Nobuo Ishida, Jun Yasuda, Masao Nagasaki, Naoki Nariai, Atsushi Endo, Kei Homma, Fumiki Katsuoka, Yoichi Matsubara, Masayuki Yamamoto, Nobuo Fuse

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　58　(5)　2818-2831　2017/05

    DOI： 10.1167/iovs.16-20646 　

    ISSN： 0146-0404

    eISSN： 1552-5783

  149. Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies Peer-reviewed

    Tsuyoshi Hachiya, Ryohei Furukawa, Yuh Shiwa, Hideki Ohmomo, Kanako Ono, Fumiki Katsuoka, Masao Nagasaki, Jun Yasuda, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto, Kozo Tanno, Mamoru Satoh, Ryujin Endo, Makoto Sasaki, Kiyomi Sakata, Seiichiro Kobayashi, Kuniaki Ogasawara, Jiro Hitomi, Kenji Sobue, Atsushi Shimizu

    NPJ GENOMIC MEDICINE　2　11　2017/04

    DOI： 10.1038/s41525-017-0016-5 　

    ISSN： 2056-7944

  150. Fixed combination of travoprost and timolol maleate reduces intraocular pressure in Japanese patients with primary open-angle glaucoma or ocular hypertension: Analysis by prostaglandin analogue Peer-reviewed

    Tadashi Nakano, Shiro Mizoue, Nobuo Fuse, Aiko Iwase, Shun Matsumoto, Keiji Yoshikawa, I.CHANGE2 study group

    Clinical Ophthalmology　11　55-61　2017/01/01

    Publisher: Dove Medical Press Ltd

    DOI： 10.2147/OPTH.S120639 　

    ISSN： 1177-5483 1177-5467

  151. Monitoring of minimal residual disease in early T-cell precursor acute lymphoblastic leukaemia by next-generation sequencing. International-journal Peer-reviewed

    Pan X, Nariai N, Fukuhara N, Saito S, Sato Y, Katsuoka F, Kojima K, Kuroki Y, Danjoh I, Saito R, Hasegawa S, Okitsu Y, Kondo A, Onishi Y, Nagami F, Kiyomoto H, Hozawa A, Fuse N, Nagasaki M, Shimizu R, Yasuda J, Harigae H, Yamamoto M

    British journal of haematology　176　(2)　318-321　2017/01

    DOI： 10.1111/bjh.13948 　

    ISSN： 0007-1048

  152. The Tohoku Medical Megabank Project: Design and Mission. Peer-reviewed

    Kuriyama S, Yaegashi N, Nagami F, Arai T, Kawaguchi Y, Osumi N, Sakaida M, Suzuki Y, Nakayama K, Hashizume H, Tamiya G, Kawame H, Suzuki K, Hozawa A, Nakaya N, Kikuya M, Metoki H, Tsuji I, Fuse N, Kiyomoto H, Sugawara J, Tsuboi A, Egawa S, Ito K, Chida K, Ishii T, Tomita H, Taki Y, Minegishi N, Ishii N, Yasuda J, Igarashi K, Shimizu R, Nagasaki M, Koshiba S, Kinoshita K, Ogishima S, Takai-Igarashi T, Tominaga T, Tanabe O, Ohuchi N, Shimosegawa T, Kure S, Tanaka H, Ito S, Hitomi J, Tanno K, Nakamura M, Ogasawara K, Kobayashi S, Sakata K, Satoh M, Shimizu A, Sasaki M, Endo R, Sobue K, Tohoku Medical Megabank, Project Study Group T, Yamamoto M

    Journal of epidemiology　26　(9)　493-511　2016/09

    DOI： 10.2188/jea.JE20150268 　

    ISSN： 0917-5040

  153. ゲノムコホート研究における遺伝を専門とする看護師の役割 遺伝情報の結果返却に関連して

    相澤 弥生, 小林 朋子, 川口 悦生, 長神 風二, 安田 純, 布施 昇男, 鈴木 洋一, 川目 裕

    日本遺伝看護学会誌　15　(1)　33-33　2016/08

    Publisher: 日本遺伝看護学会

    ISSN： 1881-3267

  154. The structural origin of metabolic quantitative diversity. International-journal Peer-reviewed

    Koshiba S, Motoike I, Kojima K, Hasegawa T, Shirota M, Saito T, Saigusa D, Danjoh I, Katsuoka F, Ogishima S, Kawai Y, Yamaguchi-Kabata Y, Sakurai M, Hirano S, Nakata J, Motohashi H, Hozawa A, Kuriyama S, Minegishi N, Nagasaki M, Takai-Igarashi T, Fuse N, Kiyomoto H, Sugawara J, Suzuki Y, Kure S, Yaegashi N, Tanabe O, Kinoshita K, Yasuda J, Yamamoto M

    Scientific reports　6　31463-31463　2016/08

    DOI： 10.1038/srep31463 　

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    Relationship between structural variants of enzymes and metabolic phenotypes in human population was investigated based on the association study of metabolite quantitative traits with whole genome sequence data for 512 individuals from a population cohort. We identified five significant associations between metabolites and non-synonymous variants. Four of these non-synonymous variants are located in enzymes involved in metabolic disorders, and structural analyses of these moderate non-synonymous variants demonstrate that they are located in peripheral regions of the catalytic sites or related regulatory domains. In contrast, two individuals with larger changes of metabolite levels were also identified, and these individuals retained rare variants, which caused non-synonymous variants located near the catalytic site. These results are the first demonstrations that variant frequency, structural location, and effect for phenotype correlate with each other in human population, and imply that metabolic individuality and susceptibility for diseases may be elicited from the moderate variants and much more deleterious but rare variants.

  155. Whole-genome Japanese Reference Panel and future directions Peer-reviewed

    Masao Nagasaki, Jun Yasuda, Fumiki Katsuoka, Naoki Nariai, Kaname Kojima, Yosuke Kawai, Yumi Yamaguchi-Kabata, Junji Yokozawa, Inaho Danjoh, Sakae Saito, Yukuto Sato, Takahiro Mimori, Kaoru Tsuda, Rumiko Saito, Pan Xiaoqing, Satoshi Nishikawa, Shin Ito, Yoko Kuroki, Osamu Tanabe, Nobuo Fuse, Shinichi Kuriyama, Hideyasu Kiyomoto, Atsushi Hozawa, Naoko Minegishi, Kengo Kinoshita, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto

    GENES & GENETIC SYSTEMS　90　(6)　377-377　2015/12

    ISSN： 1341-7568

    eISSN： 1880-5779

  156. Fixed Combination of Travoprost and Timolol Maleate Reduces Intraocular Pressure in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Prospective Multicenter Open-Label Study Peer-reviewed

    Tadashi Nakano, Shiro Mizoue, Nobuo Fuse, Aiko Iwase, Shun Matsumoto, Keiji Yoshikawa

    Advances in Therapy　32　(9)　823-837　2015/09/01

    Publisher: Springer Healthcare

    DOI： 10.1007/s12325-015-0246-9 　

    ISSN： 1865-8652 0741-238X

  157. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Peer-reviewed

    Nagasaki M, Yasuda J, Katsuoka F, Nariai N, Kojima K, Kawai Y, Yamaguchi-Kabata Y, Yokozawa J, Danjoh I, Saito S, Sato Y, Mimori T, Tsuda K, Saito R, Pan X, Nishikawa S, Ito S, Kuroki Y, Tanabe O, Fuse N, Kuriyama S, Kiyomoto H, Hozawa A, Minegishi N, Douglas Engel J, Kinoshita K, Kure S, Yaegashi N, ToMMo Japanese Reference Panel Project, Yamamoto M

    Nature communications　6　8018　2015/08

    DOI： 10.1038/ncomms9018 　

    ISSN： 2041-1723

  158. A common variant near TGFBR3 is associated with primary open angle glaucoma. International-journal Peer-reviewed

    Zheng Li, R Rand Allingham, Masakazu Nakano, Liyun Jia, Yuhong Chen, Yoko Ikeda, Baskaran Mani, Li-Jia Chen, Changwon Kee, David F Garway-Heath, Sarangapani Sripriya, Nobuo Fuse, Khaled K Abu-Amero, Chukai Huang, Prasanthi Namburi, Kathryn Burdon, Shamira A Perera, Puya Gharahkhani, Ying Lin, Morio Ueno, Mineo Ozaki, Takanori Mizoguchi, Subbiah Ramasamy Krishnadas, Essam A Osman, Mei Chin Lee, Anita S Y Chan, Liza-Sharmini A Tajudin, Tan Do, Aurelien Goncalves, Pascal Reynier, Hong Zhang, Rupert Bourne, David Goh, David Broadway, Rahat Husain, Anil K Negi, Daniel H Su, Ching-Lin Ho, Augusto Azuara Blanco, Christopher K S Leung, Tina T Wong, Azhany Yakub, Yutao Liu, Monisha E Nongpiur, Jong Chul Han, Do Nhu Hon, Balekudaru Shantha, Bowen Zhao, Jinghong Sang, NiHong Zhang, Ryuichi Sato, Kengo Yoshii, Songhomita Panda-Jonas, Allison E Ashley Koch, Leon W Herndon, Sayoko E Moroi, Pratap Challa, Jia Nee Foo, Jin-Xin Bei, Yi-Xin Zeng, Cameron P Simmons, Tran Nguyen Bich Chau, Philomenadin Ferdinamarie Sharmila, Merwyn Chew, Blanche Lim, Pansy O S Tam, Elaine Chua, Xiao Yu Ng, Victor H K Yong, Yaan Fun Chong, Wee Yang Meah, Saravanan Vijayan, Sohn Seongsoo, Wang Xu, Yik Ying Teo, Jessica N Cooke Bailey, Jae H Kang, Jonathan L Haines, Ching Yu Cheng, Seang-Mei Saw, E-Shyong Tai, Julia E Richards, Robert Ritch, Douglas E Gaasterland, Louis R Pasquale, Jianjun Liu, Jost B Jonas, Dan Milea, Ronnie George, Saleh A Al-Obeidan, Kazuhiko Mori, Stuart Macgregor, Alex W Hewitt, Christopher A Girkin, Mingzhi Zhang, Periasamy Sundaresan, Lingam Vijaya, David A Mackey, Tien Yin Wong, Jamie E Craig, Xinghuai Sun, Shigeru Kinoshita, Janey L Wiggs, Chiea-Chuen Khor, Zhenglin Yang, Chi Pui Pang, Ningli Wang, Michael A Hauser, Kei Tashiro, Tin Aung, Eranga N Vithana

    Human molecular genetics　24　(13)　3880-92　2015/07/01

    DOI： 10.1093/hmg/ddv128 　

    ISSN： 0964-6906

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    Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

  159. Eczema and Asthma Symptoms among Schoolchildren in Coastal and Inland Areas after the 2011 Great East Japan Earthquake: The ToMMo Child Health Study. Peer-reviewed

    Miyashita M, Kikuya M, Yamanaka C, Ishikuro M, Obara T, Sato Y, Metoki H, Nakaya N, Nagami F, Tomita H, Kiyomoto H, Sugawara J, Hozawa A, Fuse N, Suzuki Y, Tsuji I, Kure S, Yaegashi N, Yamamoto M, Kuriyama S

    The Tohoku journal of experimental medicine　237　(4)　297-305　2015

    DOI： 10.1620/tjem.237.297 　

    ISSN： 0040-8727

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    After the Great East Japan Earthquake of 2011, there has been a concern about health problems among children. Therefore, we investigated the prevalence of wheeze and eczema symptoms and associated factors among children in areas primarily affected by the disaster. From 2012 to 2014, we distributed the parent-administered questionnaire to 25,198 children in all 233 public schools in the 13 municipalities of Miyagi Prefecture in northeast Japan. A total of 7,155 responses (mean age 10.5 ± 2.2 years) were received (response rate: 28.4%). The prevalence of allergic symptoms according to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire in 2nd, 4th, 6th, and 8th graders was 12.4%, 9.9%, 9.3%, and 5.6% for wheeze, and 20.1%, 18.0%, 14.0%, and 12.4% for eczema. In multivariate logistic analysis, younger age, history of hospitalization, and difficulties in children's daily lives as assessed by the Strengths and Difficulties Questionnaire (SDQ), were significantly and consistently associated with both allergic symptoms (both P < 0.05). Living in a coastal municipality was also associated with eczema symptoms (P = 0.0278). The prevalence of eczema symptoms in the 2nd (20.1%) and 8th (12.4%) grades was significantly higher than previously reported in Japan. Living in a coastal municipality was independently associated with eczema symptoms, and psychometric properties were also closely linked to allergic symptoms. These findings are clinically important for understanding the risks of allergic disorders after natural disasters.

  160. Protocol and Research Perspectives of the ToMMo Child Health Study after the 2011 Great East Japan Earthquake. Peer-reviewed

    Kikuya M, Miyashita M, Yamanaka C, Ishikuro M, Sato Y, Obara T, Metoki H, Nakaya N, Nagami F, Tomita H, Kiyomoto H, Sugawara J, Hozawa A, Fuse N, Suzuki Y, Tsuji I, Kure S, Yaegashi N, Yamamoto M, Kuriyama S

    The Tohoku journal of experimental medicine　236　(2)　123-130　2015

    DOI： 10.1620/tjem.236.123 　

    ISSN： 0040-8727

    eISSN： 1349-3329

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    Residents of areas affected by the Great East Japan Earthquake may suffer from diseases or health problems. We are conducting a cross-sectional study from 2012 to 2015 to investigate and address the health needs of schoolchildren affected by this disaster. In this paper, we describe the protocol and research perspectives of our long-term child health study, and present the results obtained immediately after the disaster. The parent-administered questionnaire includes the International Study of Asthma and Allergies in Childhood questionnaire for asthma and eczema symptoms, the Strengths and Difficulties Questionnaire (SDQ), and a questionnaire on influenza infection and vaccination status. In 2012, we distributed the questionnaire to 3,505 (2nd, 4th, 6th, and 8th graders) in three municipalities located in southern coastal area among the 28 municipalities, and 1,277 (36.4%) returned the completed questionnaire. Mean age was 11.1 ± 2.2 years old. The number of children with symptoms of wheeze and eczema in the past 12 months was 146 (11.4%) and 199 (15.6%), respectively. The SDQ total difficulties score revealed 174 (13.6%) children with some form of difficulty in their daily lives. From May 2011 to April 2012, 195 (15.3%) and 649 (50.8%) children received the influenza vaccination once and twice, respectively, and 532 (41.7%) had suffered from influenza. The prevalence of eczema symptoms or some form of difficulty was higher than the Japanese average. However, careful interpretation was required because of potential self-selection bias from the low response rate. We will continue this study of schoolchildren to provide aggregate findings.

  161. 極早期緑内障病態研究 極早期緑内障眼における遺伝子多型とプロスタグランジン関連薬による乳頭循環反応

    志賀 由己浩, 布施 昇男, 清水 愛, 木村 雅恵, 津田 聡, 相澤 奈帆子, 横山 悠, 安井 朝輝, 加藤 圭一, 中澤 徹

    日本緑内障学会抄録集　25回　87-87　2014/09

    Publisher: 日本緑内障学会

  162. Validation of multiple single nucleotide variation calls by additional exome analysis with a semiconductor sequencer to supplement data of whole-genome sequencing of a human population. Peer-reviewed

    Motoike IN, Matsumoto M, Danjoh I, Katsuoka F, Kojima K, Nariai N, Sato Y, Yamaguchi-Kabata Y, Ito S, Kudo H, Nishijima I, Nishikawa S, Pan X, Saito R, Saito S, Saito T, Shirota M, Tsuda K, Yokozawa J, Igarashi K, Minegishi N, Tanabe O, Fuse N, Nagasaki M, Kinoshita K, Yasuda J, Yamamoto M

    BMC genomics　15　673　2014/08

    DOI： 10.1186/1471-2164-15-673 　

    ISSN： 1471-2164

  163. Travoprost with sofZia® preservative system lowered intraocular pressure of Japanese normal tension glaucoma with minimal side effects Peer-reviewed

    Shiro Mizoue, Tadashi Nakano, Nobuo Fuse, Aiko Iwase, Shun Matsumoto, Keiji Yoshikawa, Kiyoshi Yaoeda, Takeshi Hara, Itaru Kimura, Tairo Kimura, Hirotaka Suzumura, Toyoaki Tsumura, Mami Nanno, Shuji Matsukura, Tomihiko Tanino, Koji Nitta, Shigeki Yamabayashi, Reiko Sugimoto, Kazuya Yamagishi, Jun Kozaki, Takanori Mizoguchi, Mineo Ozaki, Kazuhiko Unoki

    Clinical Ophthalmology　8　347-354　2014/02/03

    DOI： 10.2147/OPTH.S57640 　

    ISSN： 1177-5467 1177-5483

  164. 25-Gauge Microincision Vitrectomy to Treat Vitreoretinal Disease in Glaucomatous Eyes after Trabeculectomy Peer-reviewed

    Hiroshi Kunikata, Naoko Aizawa, Nobuo Fuse, Toshiaki Abe, Toru Nakazawa

    JOURNAL OF OPHTHALMOLOGY　2014　306814　2014

    DOI： 10.1155/2014/306814 　

    ISSN： 2090-004X

    eISSN： 2090-0058

  165. Compression neuropathy caused by cancer metastasis to the optic nerve canal Peer-reviewed

    Hiroshi Tamai, Kazuyuki Ishida, Kensuke Murakami, Norio Narita, Teiji Tominaga, Nobuo Fuse

    BMC Research Notes　6　(1)　2013/12/20

    DOI： 10.1186/1756-0500-6-546 　

    ISSN： 1756-0500

  166. Effect of topical tafluprost on optic nerve head blood flow in patients with myopic disc type. Peer-reviewed

    Tsuda S, Yokoyama Y, Chiba N, Aizawa N, Shiga Y, Yasuda M, Yokokura S, Otomo T, Fuse N, Nakazawa T

    Journal of glaucoma　22　(5)　398-403　2013/06

    DOI： 10.1097/IJG.0b013e318237c8b3 　

    ISSN： 1057-0829

  167. Molecular genetic analysis of primary open-angle glaucoma, normal tension glaucoma, and developmental glaucoma for the VAV2 and VAV3 gene variants in Japanese subjects. Peer-reviewed

    Shi D, Takano Y, Nakazawa T, Mengkegale M, Yokokura S, Nishida K, Fuse N

    Biochemical and biophysical research communications　432　(3)　509-512　2013/03

    DOI： 10.1016/j.bbrc.2013.02.003 　

    ISSN： 0006-291X

  168. Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population. Peer-reviewed

    Shi D, Funayama T, Mashima Y, Takano Y, Shimizu A, Yamamoto K, Mengkegale M, Miyazawa A, Yasuda N, Fukuchi T, Abe H, Ideta H, Nishida K, Nakazawa T, Richards JE, Fuse N

    PloS one　8　(1)　e54115　2013

    DOI： 10.1371/journal.pone.0054115 　

  169. Association of Toll-like receptor 4 gene polymorphisms in Japanese subjects with primary open-angle, normal-tension, and exfoliation glaucoma. Peer-reviewed

    Takano Y, Shi D, Shimizu A, Funayama T, Mashima Y, Yasuda N, Fukuchi T, Abe H, Ideta H, Zheng X, Shiraishi A, Ohashi Y, Nishida K, Nakazawa T, Fuse N

    American journal of ophthalmology　154　(5)　825-832.e1　2012/11

    DOI： 10.1016/j.ajo.2012.03.050 　

    ISSN： 0002-9394

  170. Relation between central eight measurement points by Humphrey field analyzer and corresponding macular ganglion cell complex in glaucomatous eyes

    Azusa Ito, Yu Yokoyama, Toshifumi Asano, Chiyoko Okamura, Ryo Watanabe, Nobuo Fuse, Toru Nakazawa

    Japanese Journal of Clinical Ophthalmology　66　(9)　1319-1323　2012/09

    ISSN： 0370-5579

  171. Clinical Reasoning: A young man with progressive subcortical lesions and optic nerve atrophy Peer-reviewed

    Shoko Komatsuzaki, Osamu Sakamoto, Nobuo Fuse, Mitsugu Uematsu, Yoichi Matsubara, Toshihiro Ohura

    NEUROLOGY　79　(7)　E63-E68　2012/08

    DOI： 10.1212/WNL.0b013e3182648bb6 　

    ISSN： 0028-3878

  172. Progression of visual field defects in eyes with different optic disc appearances in patients with normal tension glaucoma. International-journal Peer-reviewed

    Nakazawa T, Shimura M, Ryu M, Himori N, Nitta F, Omodaka K, Doi H, Yasui T, Fuse N, Nishida K

    Journal of glaucoma　21　(6)　426-430　2012/08

    DOI： 10.1097/IJG.0b013e3182182897 　

    ISSN： 1057-0829

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    PURPOSE: To investigate the relationship between the optic disc appearance and the progression of visual field defects in eyes with normal tension glaucoma (NTG). METHODS: Two hundred nine patients with NTG, who were being treated with topical antiglaucoma drugs and had been followed for at least 3 years, were studied. The baseline optic disc appearance was classified into 4 types: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized cup enlargement (GE). The progression of the NTG was assessed by the slope of the mean deviations (MDs) obtained from the visual field results collected during the follow-up examinations. The baseline and mean intraocular pressures (IOPs) were also followed. RESULTS: Twenty-seven patients were placed in the FI group, 63 into the MY group, 24 into the SS group, and 43 into the GE group. Fifty-two patients (24.9%) could not be classified. There were no significant differences in the percentage reduction of the IOP among the 4 groups. The MD slope in the GE group (-0.51±0.74 dB/y) was significantly steeper than that in the other groups. Regression analyses showed that the factors most associated with the MD slope were the age in the FI (r, -0.495) and the GE (r=0.496) groups, and the relative reduction of the IOP (r=0.413) in the SS group. None of the factors in the MY group was significantly associated with the MD slope. CONCLUSIONS: The rate of progression of the field defects, the MD slope, in patients with NTG is possibly dependent on the baseline optic disc appearance. Thus, the optic disc appearance may be useful for the management of patients with NTG.

  173. [Analysis of retinal nerve fiber layer thickness in superior segmental optic hypoplasia (SSOH)]. Peer-reviewed

    Fuse N, Aizawa N, Yokoyama Y, Nakamura M, Omodaka K, Sado K, Nakazawa T

    Nippon Ganka Gakkai zasshi　116　(6)　575-580　2012/06

    Publisher:

    ISSN： 0029-0203

  174. Evaluation of CNTNAP2 gene polymorphisms for exfoliation syndrome in Japanese. International-journal Peer-reviewed

    Shimizu A, Takano Y, Shi D, Yokokura S, Yokoyama Y, Zheng X, Shiraishi A, Ohashi Y, Nakazawa T, Fuse N

    Molecular vision　18　1395-1401　2012

    eISSN： 1090-0535

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    PURPOSE: To investigate the contactin-associated protein-like 2 (CNTNAP2) gene for single-nucleotide polymorphisms (SNPs) in Japanese patients with the exfoliation syndrome (XFS). METHODS: One hundred and eight unrelated Japanese patients with the XFS, and 199 normal controls were studied. Genomic DNA was extracted from the leukocytes of the peripheral blood, and 8 SNPs, rs826802, rs1404699, rs7803992, rs700308, rs4725736, rs2107856, rs2141388, and rs6970064, were amplified by polymerase chain reaction (PCR), directly sequenced, and genotyped. RESULTS: The allele frequencies of rs1404699 (p=8.57XE-3, odds ratio (OR)=1.59, 95% confidential intervals (CI); 1,12-2.24) and rs7803992 (p=5.43XE-4, OR=1.86, 95% CI; 1.31-2.65) were statistically significantly different between XFS and controls. In addition, there were significant differences in these genotype frequencies (p=0.0197 and 1.75XE-3). The allele and the genotype frequencies of rs2107856 and rs2141388, which were statistically significant SNPs in an earlier study, were not significantly different. CONCLUSIONS: The variants, rs1404699 and rs7803992, of CNTNAP2 should be associated with XFS in the Japanese population.

  175. Irreversible optical clearing of rabbit dermis for autogenic corneal stroma transplantation Peer-reviewed

    Yuji Tanaka, Dong Shi, Akira Kubota, Yoshimasa Takano, Nobuo Fuse, Masayuki Yamato, Teruo Okano, Kohji Nishida

    BIOMATERIALS　32　(28)　6764-6772　2011/10

    DOI： 10.1016/j.biomaterials.2011.05.081 　

    ISSN： 0142-9612

  176. Outcomes of penetrating and deep anterior lamellar keratoplasty for keratoconus

    Megumi Uematsu, Shunji Yokokura, Yoshinori Oie, Yasuhiko Meguro, Takehiro Hariya, Nobuo Fuse, Kohji Nishida

    Japanese Journal of Clinical Ophthalmology　65　(9)　1413-1417　2011/09/15

    ISSN： 0370-5579

  177. 【臨床シリーズ 加齢性眼科疾患】 緑内障に対する鍼治療の効果と機序の検討

    関 隆志, 渡部, 正司, 松田, 綾音, 神谷, 哲治, 中澤, 徹, 布施, 昇男, 來須, 正幸, 高山 真

    鍼灸Osaka　27　(2)　647-651　2011/08

    Publisher:

    ISSN： 1340-6280

  178. 外傷性眼窩内血腫に対し経皮的眼窩内血腫除去術を行った1例

    津田 聡, 中村 政彦, 土井 洋, 布施 昇男

    臨床眼科　65　(7)　1143-1148　2011/07

    Publisher: (株)医学書院

    ISSN： 0370-5579

    eISSN： 1882-1308

  179. Fixating Dislocated Intraocular Lens by 25-Gauge Vitrectomy Peer-reviewed

    Hiroshi Kunikata, Nobuo Fuse, Toshiaki Abe

    OPHTHALMIC SURGERY LASERS & IMAGING　42　(4)　297-301　2011/07

    DOI： 10.3928/15428877-20110505-02 　

    ISSN： 1542-8877

  180. 東北大学病院におけるぶどう膜炎の臨床統計

    大友 孝昭, 阿部 俊明, 劉 孟林, 渡邉 亮, 津田 聡, 岡村 知世子, 千葉 真生, 布施 昇男

    臨床眼科　65　(6)　891-894　2011/06

    Publisher: (株)医学書院

    DOI： 10.11477/mf.1410103698 　

    ISSN： 0370-5579

    eISSN： 1882-1308

  181. Success Rates of Trabeculotomy for Steroid-Induced Glaucoma: A Comparative, Multicenter, Retrospective Cohort Study Peer-reviewed

    Keiichiro Iwao, Masaru Inatani, Hidenobu Tanihara

    AMERICAN JOURNAL OF OPHTHALMOLOGY　151　(6)　1047-1056　2011/06

    DOI： 10.1016/j.ajo.2010.11.028 　

    ISSN： 0002-9394

  182. Reproducibility of retinal circulation measurements obtained using laser speckle flowgraphy-NAVI in patients with glaucoma. International-journal Peer-reviewed

    Aizawa Naoko, Yokoyama Yu, Chiba Naoki, Omodaka Kazuko, Yasuda Masayuki, Otomo Takaaki, Nakamura Masahiko, Fuse Nobuo, Nakazawa Toru

    Clin Ophthalmol　5　1171-1176　2011/04

    DOI： 10.2147/OPTH.S22093 　

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    BACKGROUND: Laser speckle flowgraphy (LSFG) enables noninvasive quantification of the retinal circulation in glaucoma patients. In this study, we tested the intrasession reproducibility of LSFG-NAVI, a modified LSFG technique. METHODS: Sixty-five eyes from 33 subjects (male (M):female (F) = 17:16) with a mean age of 49.4 ± 11.2 years were examined in this study. Two parameters indicating reproducibility - the coefficient of variation (COV) and the intraclass correlation coefficient (ICC) - were analyzed three times on the same day that mean blur rate (MBR) was measured using LSFG-NAVI. The sites analyzed were the retinal artery and vein, the optic disk, and the choroid. Following classification according to the Glaucoma Hemifield Test (GHT; SITA-Standard 30-2 program), the COV and ICC were examined in patients with (GHT+; 38 eyes, M:F = 20:18, average age 48.9 ± 12.8 years) and without (GHT-; 27 eyes, M:F = 13:14, average age 50.1 ± 8.7 years) abnormal glaucomatous visual fields. RESULTS: FOR ALL SUBJECTS, THE INTRASESSION REPRODUCIBILITY OF MBR IN THE OPTIC DISK (COV: 3.4 ± 2.0; ICC: 0.95) and choroid (COV: 4.7 ± 3.4; ICC: 0.98) was excellent. The reproducibility for the retinal vein (COV: 8.4 ± 5.6, ICC: 0.90) and retinal artery (COV: 10.9 ± 9.9, ICC: 0.9) was moderate. MBRs in the optic disk had good reproducibility in both the GHT+ group (COV: 3.8 ± 2.0; ICC: 0.97) and the GHT- group (COV: 2.9 ± 2.1; ICC: 0.95). Local assessment of the optic disk in normal or glaucoma patients showed that the COVs of the quadrant optic disk areas were best in the temporal area of MBR (3.4%, 4.2%, respectively). CONCLUSION: LSFG-NAVI showed favorable reproducibility in evaluation of retinal circulation of glaucoma patients, particularly in the optic disk and choroid.

  183. Polymorphisms in ARMS2 (LOC387715) and LOXL1 Genes in the Japanese With Age-Related Macular Degeneration Peer-reviewed

    Nobuo Fuse, Mingge Mengkegale, Akiko Miyazawa, Toshiaki Abe, Toru Nakazawa, Ryosuke Wakusawa, Kohji Nishida

    AMERICAN JOURNAL OF OPHTHALMOLOGY　151　(3)　550-556　2011/03

    DOI： 10.1016/j.ajo.2010.08.048 　

    ISSN： 0002-9394

  184. Significant correlations between optic nerve head microcirculation and visual field defects and nerve fiber layer loss in glaucoma patients with myopic glaucomatous disk. Peer-reviewed

    Yokoyama Y, Aizawa N, Chiba N, Omodaka K, Nakamura M, Otomo T, Yokokura S, Fuse N, Nakazawa T

    Clinical ophthalmology (Auckland, N.Z.)　5　1721-1727　2011

    DOI： 10.2147/OPTH.S23204 　

    ISSN： 1177-5467

  185. Association between optic nerve blood flow and objective examinations in glaucoma patients with generalized enlargement disc type. International-journal Peer-reviewed

    Chiba N, Omodaka K, Yokoyama Y, Aizawa N, Tsuda S, Yasuda M, Otomo T, Yokokura S, Fuse N, Nakazawa T

    Clinical ophthalmology (Auckland, N.Z.)　5　1549-1556　2011

    DOI： 10.2147/OPTH.S22097 　

    ISSN： 1177-5467

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    BACKGROUND: The purpose of this study was to investigate the correlations between microcirculation in the optic disc, average peripapillary retinal nerve fiber layer thickness cupping parameters, and visual field defects in glaucoma patients with the generalized enlargement disc type. METHODS: A total of 38 eyes from 38 glaucoma patients with the generalized enlargement disc type were included. The microcirculation of the optic nerve head was examined with laser speckle flow graphy, and the mean blur rate in all areas, in vessel area, and in tissue area were calculated using the laser speckle flow graphy analyzer software. Average peripapillary retinal nerve fiber layer thickness was measured using Stratus optical coherence tomography, and cupping parameters were accessed using the Heidelberg retina tomograph. The mean deviation in the Humphrey field analyzer (30-2 SITA standard) was analyzed. The correlation between these parameters was evaluated using the Spearman rank correlation coefficient. RESULTS: The correlation coefficient of mean blur rate in all optic disc area to the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation were r = 0.7546 (P < 0.0001), r = -0.6208 (P < 0.0001), and r = 0.6010 (P = 0.0001), respectively. The mean blur rate in tissue area of the optic disc showed r = 0.7305 (P < 0.0001), r = -0.6438 (P < 0.0001), and r = 0.6338 (P < 0.0001). CONCLUSION: We found that the mean blur rate in the optic disc was significantly correlated with the average peripapillary retinal nerve fiber layer thickness, vertical C/D, and mean deviation in patients with the generalized enlargement disc type of glaucoma. In particular, the mean blur rate in tissue area was more highly correlated than the vessel area with other results of examination in glaucoma patients with the generalized enlargement disc type.

  186. Successful Removal of Large Intraocular Foreign Body by 25-Gauge Microincision Vitrectomy Surgery Peer-reviewed

    Hiroshi Kunikata, Megumi Uematsu, Toru Nakazawa, Nobuo Fuse

    JOURNAL OF OPHTHALMOLOGY　2011　940323-940323　2011

    DOI： 10.1155/2011/940323 　

    ISSN： 2090-004X

  187. タフルプロスト点眼による視神経乳頭循環への影響

    津田 聡, 中澤 徹, 千葉 真生, 相澤 奈緒子, 横山 悠, 小野 省太, 布施 昇男

    日本緑内障学会抄録集　21回　108-108　2010/09

    Publisher: 日本緑内障学会

  188. 手術を控えた患者さんが聞きたい5つの疑問に答える Invited Peer-reviewed

    布施昇男

    眼科ケア　919-922　2010/09

  189. Different types of optic disc shape in patients with advanced open-angle glaucoma Peer-reviewed

    Toru Nakazawa, Nobuo Fuse, Kazuko Omodaka, Naoko Aizawa, Souichiro Kuwahara, Kohji Nishida

    JAPANESE JOURNAL OF OPHTHALMOLOGY　54　(4)　291-295　2010/07

    DOI： 10.1007/s10384-010-0816-y 　

    ISSN： 0021-5155

  190. Correlation between peripapillary macular fiber layer thickness and visual acuity in patients with open-angle glaucoma. Peer-reviewed

    Omodaka Kazuko, Nakazawa Toru, Yokoyama Yu, Doi Hiroshi, Fuse Nobuo, Nishida Kohji

    Clin Ophthalmol　4　629-635　2010/04

  191. Correlation between morphology of optic disc determined by Heidelberg Retina Tomograph II and visual function in eyes with open-angle glaucoma. Peer-reviewed

    Omodaka Kazuko, Nakazawa Toru, Otomo Takaaki, Nakamura Masahiko, Fuse Nobuo, Nishida Kohji

    Clin Ophthalmol　4　765-772　2010/04

  192. Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese population Peer-reviewed

    Nobuo Fuse, Akiko Miyazawa, Kana Takahashi, Michiru Noro, Toru Nakazawa, Kohji Nishida

    JAPANESE JOURNAL OF OPHTHALMOLOGY　54　(1)　1-6　2010/01

    DOI： 10.1007/s10384-009-0769-1 　

    ISSN： 0021-5155

  193. 緑内障手術と高次収差

    布施昇男

    あたらしい眼科　57-58　2010/01

  194. Observation of posterior corneal vesicles with in vivo confocal microscopy and anterior segment OCT Peer-reviewed

    Ryou Watanabe, Toru Nakazawa, Nobuo Fuse

    Clinical Ophthalmology　4　(1)　1243-1247　2010

    DOI： 10.2147/OPTH.S14550 　

    ISSN： 1177-5467 1177-5483

  195. Japanese case of follicular lymphoma of ocular adnexa diagnosed by clinicopathologic, immunohistochemical, and molecular genetic techniques Peer-reviewed

    Takaaki Otomo, Nobuo Fuse, Kenichi Ishizawa, Motohiko Seimiya, Masahiko Shimura, Ryo Ichinohasama

    Clinical Ophthalmology　4　(1)　1397-1402　2010

    DOI： 10.2147/OPTH.S15219 　

    ISSN： 1177-5467 1177-5483

  196. Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice Peer-reviewed

    Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, Kenji Kikushima, Atsuko Kimura, Nobuo Fuse, Yoshinori Mitamura, Kuniko Kohyama, Yoh Matsumoto, Kohichi Tanaka, Takayuki Harada

    NEUROSCIENCE LETTERS　465　(2)　160-164　2009/11

    DOI： 10.1016/j.neulet.2009.09.029 　

    ISSN： 0304-3940

  197. Central retinal artery occlusion following severe blow-out fracture in young adult. International-journal Peer-reviewed

    Noriko Himori, Hiroshi Kunikata, Takaaki Otomo, Nobuo Fuse, Kohji Nishida

    Clinical ophthalmology (Auckland, N.Z.)　3　325-8　2009

    ISSN： 1177-5467

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    A 20-year-old woman was involved in a traffic accident while riding a motorcycle. The vision in her right eye was severely reduced. At the first examination, the eyelids of her right eye were severely swollen, and the eye could barely be seen. The fundus was not visible. She had no light perception in her vision. Computed tomography revealed a severe blow-out fracture in her right eye. Surgery was immediately performed to correct the fracture and the eye globe was replaced in the orbit. On the fourth postoperative day, the right fundus was visible and a cherry-red spot and milky-white edema were seen. Fluorescein angiography showed an arterial filling defect. Four months later, her visual acuity was light perception. Our case shows that a central retinal artery occlusion can be a complication of a blow-out fracture of the lower orbital wall and can lead to severe visual loss even with early surgical repair.

  198. Evaluation of LOXL1 polymorphism in eyes with exfoliation glaucoma in Japanese Peer-reviewed

    Nobuo Fuse, Akiko Miyazawa, Toru Nakazawa, MingGe Mengkegale, Takaaki Otomo, Kohji Nishida

    MOLECULAR VISION　14　(161-62)　1338-1343　2008/07

    ISSN： 1090-0535

  199. Presence of myocilin sequence variants in Japanese patients with open-angle glaucoma. Peer-reviewed

    Mengkegale MingGe, Fuse Nobuo, Miyazawa Akiko, Takahashi Kana, Seimiya Motohiko, Yasui Tomoki, Tamai Makoto, Nakazawa Toru, Nishida Kohji

    Mol Vis　14　413-417　2008/04

  200. ICDからみた真菌感染対策―診断から治療までの総合戦略― Peer-reviewed

    赤坂純逸, 布施昇男, 佐々木淳一, 金光敬二, 田林光一, 篠澤洋太郎, 賀来満夫

    化学療法の領域　83　2007/07

  201. コントラスト感度視力検査装置による緑内障患者に対する鍼治療の視機能評価 Peer-reviewed

    相良淑子, 布施昇男, 関隆志, 中澤徹, 高橋佳奈, 清宮基彦, 横倉俊二, 来須正幸, 西田幸二

    眼科臨床医報　101　(6)　715-718　2007/06

    Publisher:

    ISSN： 0386-9601

  202. Novel mutations in the FOXC1 gene in Japanese patients with Axenfeld-Rieger syndrome. Peer-reviewed

    Fuse Nobuo, Takahashi Kana, Yokokura Shunji, Nishida Kohji

    Mol Vis　13　1005-1009　2007/04

  203. Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese. Peer-reviewed

    Miyazawa Akiko, Fuse Nobuo, Mengkegale MingGe, Ryu Morin, Seimiya Motohiko, Wada Yuko, Nishida Kohji

    Mol Vis　13　1912-1919　2007/04

  204. 緑内障3分診療を科学する！？youngsterの乳頭を診る？ Peer-reviewed

    吉川啓司, 松元俊, 鵜木一彦, 前田秀高, 布施昇男

    眼科　49　(3)　339-356　2007/03

    Publisher:

    ISSN： 0016-4488

  205. Pitavastatin prevents NMDA-induced retinal ganglion cell death by suppressing leukocyte recruitment Peer-reviewed

    Toru Nakazawa, Hidetoshi Takahashi, Kazuaki Nishijima, Masahiko Shimura, Nobuo Fuse, Makoto Tamai, Ali Hafezi-Moghadam, Kohji Nishida

    JOURNAL OF NEUROCHEMISTRY　100　(4)　1018-1031　2007/02

    DOI： 10.1111/j.1471-4159.2006.04274.x 　

    ISSN： 0022-3042

  206. Hypothermia protects cultured human retinal pigment epithelial cells against indocyanine green toxicity Peer-reviewed

    Hiroshi Kunikata, Hiroshi Tomita, Toshiaki Abe, Hiromi Murata, Yoshiko Sagara, Hajime Sato, Yuko Wada, Nobuo Fuse, Yoichi Nakagawa, Makoto Tamai, Kohji Nishida

    JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS　23　(1)　35-39　2007/02

    DOI： 10.1089/jop.2006.0072 　

    ISSN： 1080-7683

    eISSN： 1557-7732

  207. SNPs and interaction analyses of Noelin 2, myocilin, and optineurin genes in Japanese patients with open-angle glaucoma Peer-reviewed

    Tomoyo Funayama, Yukihiko Mashima, Yuichiro Ohtake, Karin Ishikawa, Nobuo Fuse, Noriko Yasuda, Takeo Fukuchi, Akira Murakami, Yoshihiro Hotta, Naoki Shimada

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　47　(12)　5368-5375　2006/12

    DOI： 10.1167/iovs.06-0196 　

    ISSN： 0146-0404

  208. Polymorphisms in Complement factor H and Hemicentin-1 genes in a Japanese population with dry-type age-related macular degeneration Peer-reviewed

    Nobuo Fuse, Akiko Miyazawa, MingGe Mengkegale, Madoka Yoshida, Ryosuke Wakusawa, Toshiaki Abe, Makoto Tamai

    AMERICAN JOURNAL OF OPHTHALMOLOGY　142　(6)　1074-1076　2006/12

    DOI： 10.1016/j.ajo.2006.07.030 　

    ISSN： 0002-9394

  209. Neuroprotective effect of latanoprost on rat retinal ganglion cells Peer-reviewed

    Hideyo Kudo, Toru Nakazawa, Masahiko Shimura, Hidetoshi Takahashi, Nobuo Fuse, Kenji Kashiwagi, Makoto Tamai

    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY　244　(8)　1003-1009　2006/08

    DOI： 10.1007/s00417-005-0215-0 　

    ISSN： 0721-832X

  210. Paraoxonase 1 gene polymorphisms influence clinical features of open-angle glaucoma Peer-reviewed

    Yoko Inagaki, Yukihiko Mashima, Tomoyo Funayama, Yuichiro Ohtake, Nobuo Fuse, Noriko Yasuda, Takeo Fukuchi, Akira Murakami, Yoshihiro Hotta

    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY　244　(8)　984-990　2006/08

    DOI： 10.1007/s00417-005-0200-7 　

    ISSN： 0721-832X

  211. Visual function with acupuncture tested by visual evoked potential Peer-reviewed

    Yoshiko Sagara, Nobuo Fuse, Motohiko Seimiya, Syunji Yokokura, Kei Watanabe, Toru Nakazawa, Masayuki Kurusu, Takashi Seki, Makoto Tamai

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　209　(3)　235-241　2006/07

    DOI： 10.1620/tjem.209.235 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  212. Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in families with earlier adult age at diagnosis Peer-reviewed

    A Woodroffe, CM Krafchak, N Fuse, PR Lichter, SE Moroi, R Schertzer, CA Downs, WL Duren, M Boehnke, JE Richards

    EXPERIMENTAL EYE RESEARCH　82　(6)　1068-1074　2006/06

    DOI： 10.1016/j.exer.2005.10.008 　

    ISSN： 0014-4835

  213. 眼所見を認めたブルートウー症候群の1例 Peer-reviewed

    番裕美子, 國方彦志, 松永直子, 中山恵輔, 宮田正弘, 布施昇男, 中川陽一

    眼科　48　(5)　805-808　2006/05

    ISSN： 0016-4488

  214. Hypothermia of 8 degrees C protects cultured retinal pigment epithelial cells and retinal ganglion cells against trypan blue toxicity Peer-reviewed

    H Kunikata, T Abe, H Murata, Y Sagara, R Wakusawa, H Sato, M Yoshida, N Fuse, M Tamai

    AMERICAN JOURNAL OF OPHTHALMOLOGY　141　(4)　754-756　2006/04

    DOI： 10.1016/j.ajo.2005.10.054 　

    ISSN： 0002-9394

  215. Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma. Peer-reviewed

    Inagaki Yoko, Mashima Yukihiko, Fuse Nobuo, Funayama Tomoyo, Ohtake Yuichiro, Yasuda Noriko, Murakami Akira, Hotta Yoshihiro, Fukuchi Takeo, Tsubota Kazuo

    Mol Vis　12　673-680　2006/04

  216. 若年患者における網膜中心動脈閉塞の1例 Peer-reviewed

    渡邉亮, 國方彦志, 布施昇男

    眼科　48　(3)　379-384　2006/03

    Publisher:

    ISSN： 0016-4488

  217. Mitochondrial DNA mutations with Leber's hereditary optic neuropathy in Japanese patients with open-angle glaucoma Peer-reviewed

    Y Inagaki, Y Mashima, N Fuse, Y Ohtake, T Fujimaki, J Fukuchi

    JAPANESE JOURNAL OF OPHTHALMOLOGY　50　(2)　128-134　2006/03

    DOI： 10.1007/s10384-005-0290-0 　

    ISSN： 0021-5155

  218. Hypothermia protects cultured human retinal pigment epithelial cells against trypan blue toxicity Peer-reviewed

    H Kunikata, H Tomita, H Murata, Y Sagara, H Sato, Y Wada, N Fuse, Y Nakagawa, T Abe, M Tamai

    OPHTHALMOLOGICA　220　(2)　114-117　2006

    DOI： 10.1159/000090576 　

    ISSN： 0030-3755

  219. Acupuncture for patients with glaucoma Peer-reviewed

    Masayuki Kurusu, Kei Watanabe, Toru Nakazawa, Takashi Seki, Hiroyuki Arai, Hidetada Sasaki, Nobuo Fuse, Makoto Tamai

    EXPLORE-THE JOURNAL OF SCIENCE AND HEALING　1　(5)　372-376　2005/09

    DOI： 10.1016/j.explore.2005.06.007 　

    ISSN： 1550-8307

  220. A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10 Peer-reviewed

    S Shimizu, C Krafchak, N Fuse, MP Epstein, MT Schteingart, A Sugar, M Eibschitz-Tsimhoni, CA Downs, F Rozsa, EH Trager, DM Reed, M Boehnke, SE Moroi, JE Richards

    AMERICAN JOURNAL OF MEDICAL GENETICS PART A　130A　(4)　372-377　2004/11

    DOI： 10.1002/ajmg.a.30267 　

    ISSN： 0148-7299

  221. A locus for Posterior Polymorphous Corneal Dystrophy (PPCD3) maps to chromosome 10 Peer-reviewed

    Satoko Shimizu, Charles Krafchak, Nobuo Fuse, Michael P. Epstein, Miriam T. Schteingart, Alan Sugar, Maya Eibschitz-Tsimhoni, Catherine A. Downs, Frank Rozsa, Edward H. Trager, David M. Reed, Michael Boehnke, Sayoko E. Moroi, Julia E. Richards

    American Journal of Medical Genetics　130　(4)　372-377　2004/11/01

    DOI： 10.1002/ajmg.a.30267 　

    ISSN： 1552-4825

  222. Molecular genetic analysis of optineurin gene for primary open-angle and normal tension glaucoma in the Japanese population Peer-reviewed

    N Fuse, K Takahashi, H Akiyama, T Nakazawa, M Seimiya, S Kuwahara, M Tamai

    JOURNAL OF GLAUCOMA　13　(4)　299-303　2004/08

    DOI： 10.1097/00061198-200408000-00007 　

    ISSN： 1057-0829

  223. Clinicopathologic correlation and genetic analysis in a case of posterior polymorphous corneal dystrophy Peer-reviewed

    SE Moroi, PA Gokhale, MT Schteingart, A Sugar, CA Downs, S Shimizu, C Krafchak, N Fuse, SG Elner, VM Elner, A Flint, MP Epstein, M Boehnke, JE Richards

    AMERICAN JOURNAL OF OPHTHALMOLOGY　135　(4)　461-470　2003/04

    DOI： 10.1016/S0002-9394(02)02032-9 　

    ISSN： 0002-9394

  224. Evaluation of visual function in advanced glaucoma using a low vision evaluator stimulated with red, blue and green lights

    Kana Takahashi, Yoichi Nakagawa, Soichiro Kuwahara, Nobuo Fuse, Hiroshi Akiyama, Toru Nakazawa, Yumiko Ban, Makoto Tamai

    Japanese Journal of Clinical Ophthalmology　57　(7)　1257-1260　2003

    ISSN： 0370-5579

  225. Intraocular hemangiopericytoma - A case report Peer-reviewed

    M Shimura, K Suzuki, N Fuse, M Yoshida, Y Saiki, H Ohtani, M Tamai

    OPHTHALMOLOGICA　215　(5)　378-382　2001/09

    DOI： 10.1159/000050890 　

    ISSN： 0030-3755

  226. A frequent 1085delC/insGAAG mutation in the RDH5 gene in Japanese patients with fundus albipunctatus Peer-reviewed

    Y Wada, T Abe, N Fuse, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　41　(7)　1894-1897　2000/06

    ISSN： 0146-0404

  227. Auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration: Short-term results Peer-reviewed

    T Abe, M Yoshida, H Tomita, T Kano, M Sato, Y Wada, N Fuse, T Yamada, M Tamai

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　191　(1)　7-20　2000/05

    ISSN： 0040-8727

    eISSN： 1349-3329

  228. Molecular genetic analysis of ABCR gene in Japanese dry form age-related macular degeneration Peer-reviewed

    N Fuse, T Suzuki, Y Wada, M Yoshida, M Shimura, T Abe, M Nakazawa, M Tamai

    JAPANESE JOURNAL OF OPHTHALMOLOGY　44　(3)　245-249　2000/05

    DOI： 10.1016/S0021-5155(00)00150-7 　

    ISSN： 0021-5155

  229. mRNA expression of proto-oncogenes and platelet-derived growth factor in proliferative vitreoretinal diseases Peer-reviewed

    GY Ren, N Fuse, T Abe, M Tamai

    JAPANESE JOURNAL OF OPHTHALMOLOGY　44　(3)　308-311　2000/05

    DOI： 10.1016/S0021-5155(00)00149-0 　

    ISSN： 0021-5155

  230. Structural organization of the human microphthalmia-associated transcription factor gene containing four alternative promoters Peer-reviewed

    T Udono, K Yasumoto, K Takeda, S Amae, K Watanabe, H Saito, N Fuse, M Tachibana, K Takahashi, M Tamai, S Shibahara

    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION　1491　(1-3)　205-219　2000/04

    DOI： 10.1016/S0167-4781(00)00051-8 　

    ISSN： 0167-4781

  231. Visual outcome of rupture of the eyeball

    Z. Zhang, N. Fuse, M. Tamai

    Japanese Journal of Clinical Ophthalmology　54　(4)　729-733　2000

    ISSN： 0370-5579

  232. Infiltration of the optic nerve as the initial sign of recurrence in a case of acute myelogenous leukemia in the remission stage

    A. Sato, N. Fuse, H. Kunikata, Y. Nakagawa, M. Tamai

    Japanese Journal of Clinical Ophthalmology　54　(10)　1697-1701　2000

    ISSN： 0370-5579

  233. Effective treatment with topical cyclosporin A of a patient with Cogan syndrome Peer-reviewed

    Masahiko Shimura, Kanako Yasuda, Nobuo Fuse, Mitsuru Nakazawa, Makoto Tamai

    Ophthalmologica　214　(6)　429-432　2000

    Publisher: S. Karger AG

    DOI： 10.1159/000027538 　

    ISSN： 0030-3755

  234. 移植医療 眼科領域における移植医療 眼底疾患に対する細胞移植

    阿部 俊明, 富田 浩史, 吉田 まどか, 鹿野 哲也, 大橋 利吏, 佐藤 雅美, 和田 裕子, 布施 昇男, 玉井 信

    日本医学会総会会誌　25回　(II)　461-461　1999/12

    Publisher: 日本医学会

  235. Molecular cloning of cDNA encoding a novel microphthalmia-associated transcription factor isoform with a distinct amino-terminus Peer-reviewed

    Nobuo Fuse, Ken-Ichi Yasumoto, Kazuhisa Takeda, Shintaro Amae, Miki Yoshizawa, Tetsuo Udono, Kazuhiro Takahashi, Makoto Tamai, Yasushi Tomita, Masayoshi Tachibana, Shigeki Shibahara

    Journal of Biochemistry　126　(6)　1043-1051　1999

    Publisher: Japanese Biochemical Society

    DOI： 10.1093/oxfordjournals.jbchem.a022548 　

    ISSN： 0021-924X

  236. Functional analysis after auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration Peer-reviewed

    Toshiaki Abe, Madoka Yoshida, Hiroshi Tomita, Tetsuya Kano, Yoichi Nakagawa, Masami Sato, Yuko Wada, Nobuo Fuse, Tasuku Yamada, Makoto Tamai

    Tohoku Journal of Experimental Medicine　189　(4)　295-305　1999

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.189.295 　

    ISSN： 0040-8727

  237. Implications of isoform multiplicity of microphthalmia-associated transcription factor in the pathogenesis of auditory-pigmentary syndromes Peer-reviewed

    Shigeki Shibahara, Ken-Ichi Yasumoto, Shintaro Amae, Nobuo Fuse, Tetsuo Udono, Kazuhiro Takahashi

    Journal of Investigative Dermatology Symposium Proceedings　4　(2)　101-104　1999

    ISSN： 1087-0024

  238. Identification of a novel isoform of microphthalmia-associated transcription factor that is enriched in retinal pigment epithelium. Peer-reviewed

    Amae S Fuse, N, Yasumoto K Sato, S, Yajima I, Yamamoto, H, Udono, T, Durlu YK, Tamai M Takahashi, K, Shibahara S

    Biochem Biophys Res Commun.　3　(247)　710-715　1998/04

    DOI： 10.1006/bbrc.1998.8838 　

  239. Role of neurofibromin in modulation of expression of the tyrosinase-related protein 2 gene Peer-reviewed

    Hiroyuki Suzuki, Kazuhiro Takahashi, Ken-Ichi Yasumoto, Shintaro Amae, Miki Yoshizawa, Nobuo Fuse, Shigeki Shibahara

    Journal of Biochemistry　124　(5)　992-998　1998

    Publisher: Japanese Biochemical Society

    DOI： 10.1093/oxfordjournals.jbchem.a022218 　

    ISSN： 0021-924X

  240. Identification of a melanocyte-type promoter of the microphthalmia-associated transcription factor gene Peer-reviewed

    Nobuo Fuse, Ken-Ichi Yasumoto, Hiroyuki Suzuki, Kazuhiro Takahashi, Shigeki Shibahara

    Biochemical and Biophysical Research Communications　219　(3)　702-707　1996/02/27

    Publisher: Academic Press Inc.

    DOI： 10.1006/bbrc.1996.0298 　

    ISSN： 0006-291X

  241. Differential tissue-specific expression of neurofibromin isoform mRNAs in rat Peer-reviewed

    Hiroyuki Suzuki, Kazuhiro Takahashi, Ken-Ichi Yasumoto, Nobuo Fuse, Shigeki Shibahara

    Journal of Biochemistry　120　(5)　1048-1054　1996

    Publisher: Oxford University Press

    DOI： 10.1093/oxfordjournals.jbchem.a021498 　

    ISSN： 0021-924X

Show all ︎Show first 5

Misc. 96

  1. Association of Blood Eosinophil Counts with Risk of PRISm Transition: Findings from the Tohoku Medical Megabank Community-Based Cohort Study

    岩崎史, 中谷久美, 山田充啓, 中谷直樹, 小暮真奈, 畑中里衣子, 千葉一平, 高瀬雅仁, 時岡紗由里, 布施昇男, 寳澤篤, 杉浦久敏

    日本呼吸器学会誌(Web)　14　2025

    ISSN： 2186-5884

  2. 心血管疾患危険因子と大脳白質病変変化の関連:TMM計画地域住民コホート調査

    佐竹芽久美, 千葉一平, 中谷直樹, 森菜緒子, 布施昇男, 木下賢吾, 泉陽子, 麦倉俊司, 寳澤篤

    日本老年医学会雑誌(Web)　62　2025

    ISSN： 0300-9173

  3. Related Factors for Axial Length Shortening in Adults Over a 3.5-Year Follow-up

    西村尭幸, 國方彦志, 千葉一平, 中谷直樹, 寶澤篤, 布施昇男, 布施昇男, 中澤徹

    日本眼科学会雑誌　129　2025

    ISSN： 0029-0203

  4. ソルセイブによる塩味味覚閾値と高血圧有病の関連:東北メディカル・メガバンク計画地域住民コホート調査

    平田朱音, 小暮真奈, 小暮真奈, 畑中里衣子, 畑中里衣子, 中谷久美, 中谷久美, 千葉一平, 千葉一平, 高瀬雅仁, 高瀬雅仁, 布施昇男, 布施昇男, 泉陽子, 中谷直樹, 中谷直樹, 寳澤篤, 寳澤篤

    日本循環器病予防学会誌　60　(2)　2025

    ISSN： 1346-6267

  5. Fitbitを用いた身体活動および睡眠状態の測定-進捗と測定値の特性-

    千葉一平, 千葉一平, 中谷直樹, 中谷直樹, 小暮真奈, 小暮真奈, 中谷久美, 中谷久美, 畑中里衣子, 畑中里衣子, 高瀬雅仁, 高瀬雅仁, 時岡紗由理, 時岡紗由理, 小原拓, 小原拓, 小原拓, 永家聖, 永家聖, 荻島創一, 荻島創一, 荻島創一, 麦倉俊司, 麦倉俊司, 麦倉俊司, 布施昇男, 布施昇男, 布施昇男, 長神風二, 長神風二, 長神風二, 寳澤篤, 寳澤篤

    日本公衆衛生学会総会抄録集(CD-ROM)　83rd　2024

  6. ToMMo地域住民コホートにおける閉塞性換気障害の有病と関連要因,生命予後の検討

    岩崎史, 山田充啓, 中谷久美, 中谷直樹, 中村智洋, 中村智洋, 永家聖, 荻島創一, 小原拓, 布施昇男, 泉陽子, 栗山進一, 栗山進一, 杉浦久敏, 寶澤篤

    日本公衆衛生学会総会抄録集(CD-ROM)　83rd　2024

  7. 東北メディカル・メガバンク計画 地域住民コホート調査(宮城) これまでの進捗

    中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 石黒 真美, 大類 真嗣, 野田 あおい, 篠田 元気, 小原 拓, 宇留野 晃, 布施 昇男, 泉 陽子, 栗山 進一, 寳澤 篤

    Journal of Epidemiology　34　(Suppl.)　133-133　2024/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  8. ToMMo地域住民コホート調査におけるPreserved ratio impairment spirometryの有病と関連する要因の検討

    岩崎 史, 中谷 久美, 山田 充啓, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 千葉 一平, 菅野 郁美, 小原 拓, 石黒 真美, 大類 真嗣, 永家 聖, 中村 智洋, 荻島 創一, 布施 昇男, 泉 陽子, 栗山 進一, 杉浦 久敏, 寳澤 篤

    Journal of Epidemiology　34　(Suppl.)　139-139　2024/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  9. Genome-wide association study of central corneal thickness in the cohort Study

    布施昇男, 安澤隼人, 元池育子, 櫻井美由紀, 木下賢吾, 山本雅之

    日本眼科学会雑誌　128　2024

    ISSN： 0029-0203

  10. Relationship between MRI hippocampus volume and OCTA parameters

    高田菜生子, 橋本和軌, 二宮高洋, 前川重人, 石川誠, 國方彦志, 布施昇男, 麦倉俊司, 中澤徹

    日本眼科学会雑誌　128　2024

    ISSN： 0029-0203

  11. 父母と小児の眼科的検査値の関連:三世代コホート調査

    石黒真美, 小原拓, 野田あおい, 篠田元気, 大類真嗣, 宇留野晃, 吉田清香, 高田菜生子, 藤岡俊亮, 西村尭幸, 中澤徹, 布施昇男, 布施昇男, 栗山進一, 栗山進一

    日本疫学会学術総会講演集(Web)　34th　2024

  12. Integration of Mobile Health and Biobank to Establish the Dry Eye Data Platform

    赤崎安序, 赤崎安序, 布施昇男, 荻島創一, 宇留野晃, 清水厚志, 中村智洋, 長神風二, 中村正裕, 中村正裕, 清田純, 江口敦子, 猪俣明恵, 村上晶, 村上晶, 猪俣武範, 猪俣武範, 猪俣武範, 猪俣武範

    日本眼科学会雑誌　127　2023

    ISSN： 0029-0203

  13. 脳構造MRI画像を用いた神経疾患の年齢予測の検証

    松島 斗真, 吉永 健二, 高村 恒人, 舞草 伯秀, 麦倉 俊司, 森 菜緒子, 布施 昇男, 関口 敦, 阿部 十也, 花川 隆

    臨床神経生理学　50　(5)　417-417　2022/10

    Publisher: (一社)日本臨床神経生理学会

    ISSN： 1345-7101

    eISSN： 2188-031X

  14. 年齢と骨梁面積率との関連 年齢階級別の検討 ToMMo地域住民コホート調査

    菅野 郁美, 中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 中村 智洋, 小原 拓, 目時 弘仁, 布施 昇男, 栗山 進一, 辻 一郎, 寳澤 篤

    日本公衆衛生学会総会抄録集　81回　203-203　2022/09

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  15. 東北メディカル・メガバンク計画・地域住民コホート調査詳細三次調査(宮城)の進捗

    中谷 直樹, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 菅野 郁美, 小原 拓, 中村 智洋, 宇留野 晃, 布施 昇男, 泉 陽子, 丹野 高三, 辻 一郎, 栗山 進一, 寳澤 篤

    東北公衆衛生学会誌　(71)　28-28　2022/07

    Publisher: 東北公衆衛生学会

    ISSN： 0915-549X

  16. ゲノムコホート研究におけるBRCA1/2病的バリアント保持者への遺伝情報回付:遺伝情報回付による心理的・社会的影響の解析

    大根田絹子, 濱中洋平, 濱中洋平, 川目裕, 川目裕, 鈴木洋一, 鈴木洋一, 長神風二, 長神風二, 布施昇男, 布施昇男, 山本雅之, 山本雅之

    日本人類遺伝学会大会プログラム・抄録集　67th (CD-ROM)　2022

  17. Exploration of BRCA1/2 gene variants in a general population cohort and return of genomic results to the participants

    徳永英樹, 安田純, 島田宗昭, 濱中洋平, 重田昌吾, 布施昇男, 勝岡史城, 荻島創一, 荻島創一, 山口由美, 寳澤篤, 川目裕, 大根田絹子, 青木洋子, 山本雅之, 八重樫伸生

    日本癌学会学術総会抄録集(Web)　81st　2022

  18. 東北メディカル・メガバンク計画・地域住民コホート調査詳細三次調査(宮城)の概要

    中谷 直樹, 小暮 真奈, 畑中 里衣子, 菅野 郁美, 中谷 久美, 小原 拓, 中村 智洋, 宇留野 晃, 布施 昇男, 泉 陽子, 丹野 高三, 辻 一郎, 栗山 進一, 呉 繁夫, 寳澤 篤

    日本公衆衛生学会総会抄録集　80回　219-219　2021/11

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  19. ゲノムコホート研究参加者へのBRCA1/2遺伝情報回付の取り組み

    大根田絹子, 濱中洋平, 濱中洋平, 川目裕, 川目裕, 鈴木洋一, 鈴木洋一, 長神風二, 布施昇男, 布施昇男, 山本雅之, 山本雅之

    日本人類遺伝学会大会プログラム・抄録集　66th (CD-ROM)　2021

  20. 原発開放隅角緑内障におけるシュレム管の発育異常

    濱中輝彦, 櫻井哲郎, 石田誠夫, 布施昇男, 熊坂利夫

    2020/04/18

  21. Carodid Echography measured in Tohoku Medical Megabank Project

    寳澤篤, 土屋菜歩, 中村智洋, 宇留野晃, 栗山進一, 菅原準一, 呉繁夫, 布施昇男, 山本雅之

    超音波医学 Supplement　47　2020

    ISSN： 1881-9311

  22. 東北メディカル・メガバンク計画における遺伝情報返却の課題

    濱中洋平, 濱中洋平, 大根田絹子, 布施昇男, 川目裕, 川目裕, 長神風二, 鈴木吉也, 鈴木洋一, 鈴木洋一, 佐藤政文, 平塚真弘, 櫻井美佳, 宇留野晃, 山口由美, 平良摩紀子, 山本雅之, 濱中洋平, 濱中洋平

    日本人類遺伝学会大会プログラム・抄録集　65th (CD-ROM)　2020

  23. ゲノムコホート調査参加者に対するゲノム薬理学(PGx)遺伝情報の返却(回付)-PGxの知識・理解に関する調査票解析

    大根田絹子, 布施昇男, 川目裕, 川目裕, 長神風二, 鈴木吉也, 鈴木洋一, 鈴木洋一, 佐藤政文, 櫻井美佳, 宇留野晃, 濱中洋平, 平良摩紀子, 平塚真弘, 山本雅之, 山本雅之

    日本人類遺伝学会大会プログラム・抄録集　65th (CD-ROM)　2020

  24. The correlation between birth weight and %FEV1 in people in their 20s; exploring the factors influencing lung function based on Tohoku Medical Megabank Organization community health survey

    大江崇, 山田充啓, 杉浦久敏, 布施昇男, 寳澤篤, 中村智洋, 山本雅之, 一ノ瀬正和

    日本呼吸器学会誌(Web)　9　2020

    ISSN： 2186-5884

  25. 大規模ゲノムコホート調査におけるBRCA1/2遺伝子の病的バリアント保持者への遺伝情報回付に関する課題

    濱中 洋平, 石田 孝宣, 布施 昇男, 川目 裕, 山口 由美, 安田 純, 多田 寛, 宮下 穣, 原田 成美, 佐藤 章子, 青木 洋子, 長神 風二, 八重樫 伸生, 木下 賢吾, 呉 繁夫, 山本 雅之

    日本乳癌学会総会プログラム抄録集　27回　332-332　2019/07

    Publisher: (一社)日本乳癌学会

  26. Estimating frequency of pathogenic variants in a Japanese population by using the whole-genome reference panel of ToMMo

    Yumi Yamaguchi-Kabata, Jun Yasuda, Osamu Tanabe, Yoichi Suzuki, Hiroshi Kawame, Nobuo Fuse, Masao Nagasaki, Yosuke Kawai, Kaname Kojima, Fumiki Katsuoka, Sakae Saito, Inaho Danjoh, Ikuko N. Motoike, Riu Yamashita, Seizo Koshiba, Daisuke Saigusa, Gen Tamiya, Shigeo Kure, Nobuo Yaegashi, Yoshio Kawaguchi, Fuji Nagami, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Atsushi Hozawa, Soichi Ogishima, Hideyasu Kiyomoto, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto

    HUMAN GENOMICS　12　2018/03

    ISSN： 1473-9542

    eISSN： 1479-7364

  27. 東北メディカル・メガバンク地域住民コホート調査に基づく、日本人呼気一酸化窒素濃度の分布と影響因子の解析(中間報告)

    山田 充啓, 杉浦 久敏, 布施 昇男, 寳澤 篤, 高井 貴子, 土屋 奈歩, 光根 歩, 栗山 進一, 山本 雅之, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　213-213　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  28. 【ヒト疾患のデータベースとバイオバンク 情報をどう使い、どう活かすか?ゲノム医療をどう実現するか?】 (第2章)疾患データベースとバイオバンク プロジェクトの最前線と利用の実践ガイド 東北メディカル・メガバンク計画 震災復興からのコホートと次世代型バイオバンク構築

    清水 厚志, 布施 昇男

    実験医学　35　(17)　2851-2860　2017/11

    Publisher: (株)羊土社

    ISSN： 0288-5514

  29. 遺伝と遺伝性疾患に関する講習会 ゲノムコホート研究における個人への遺伝情報の回付に関するパイロット研究参加者への試み

    徳富 智明, 清水 厚志, 福島 明宗, 山本 佳世乃, 石垣 泰, 川目 裕, 長神 風二, 小林 朋子, 相澤 弥生, 沼田 早苗, 鈴木 洋一, 布施 昇男, 菅原 敦子, 中山 文予, 山本 雅之, 佐々木 真理

    日本遺伝カウンセリング学会誌　38　(2)　144-144　2017/05

    Publisher: 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  30. 早発型発達緑内障における原因遺伝子の探索

    布施 昇男, 木村 雅恵, 清水 愛, 河合 洋介, 小島 要, 長崎 正朗, 濱中 輝彦, 石田 誠夫, 中村 誠, 酒井 寛, 池田 陽子, 森 和彦, 中澤 徹, 勝岡 史城, 安田 純, 山本 雅之

    日本眼科学会雑誌　121　(臨増)　227-227　2017/03

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  31. 東北メディカル・メガバンク事業 地域住民コホート調査の詳細とドルーゼン解析調査

    本間 慶, 布施 昇男, 高井 貴子, 清元 秀泰, 菅原 純一, 鈴木 洋一, 菊谷 昌浩, 栗山 進一, 寳澤 篤, 八重樫 伸生, 呉 繁夫, 山本 雅之

    眼科臨床紀要　9　(11)　926-926　2016/11

    Publisher: 眼科臨床紀要会

    ISSN： 1882-5176

  32. 三世代コホート調査の進捗について

    目時 弘仁, 石黒 真美, 小原 拓, 佐藤 ゆき, 菊谷 昌浩, 栗山 進一, 寳澤 篤, 大隅 典子, 清元 秀泰, 菅原 準一, 鈴木 洋一, 冨永 悌二, 布施 昇男, 峯岸 直子, 辻 一郎, 呉 繁夫, 八重樫 伸生, 山本 雅之

    宮城県公衆衛生学会会誌　(48)　10-10　2016/03

    Publisher: 宮城県公衆衛生学会

    ISSN： 0912-747X

  33. 東日本大震災後の宮城県沿岸部における治療中断東北メディカル・メガバンク事業 地域住民コホート調査

    中谷 直樹, 中村 智洋, 土屋 菜歩, 成田 暁, 小暮 真奈, 中谷 純, 峯岸 直子, 布施 昇男, 鈴木 洋一, 菅原 準一, 菊谷 昌浩, 富田 博秋, 清元 秀泰, 栗山 進一, 辻 一郎, 呉 繁夫, 山本 雅之, 寳澤 篤, 丹野 高三, 佐々木 亮平, 坂田 清美

    宮城県公衆衛生学会会誌　(48)　11-11　2016/03

    Publisher: 宮城県公衆衛生学会

    ISSN： 0912-747X

  34. 東北メディカル・メガバンク事業 地域住民コホート調査における眼軸長検査

    布施 昇男, 本間 慶, 高井 貴子, 荻島 創一, 清元 秀泰, 菅原 準一, 鈴木 洋一, 菊谷 昌浩, 栗山 進一, 寳澤 篤, 八重樫 伸生, 呉 繁夫, 山本 雅之

    日本眼科学会雑誌　120　(臨増)　200-200　2016/03

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  35. 三世代コホート調査の進捗と子どもの父母の質問票

    目時弘仁, 石黒真美, 石黒真美, 小原拓, 小原拓, 佐藤ゆき, 水野聖士, 水野聖士, 宮下真子, 宮下真子, 菊谷昌浩, 菊谷昌浩, 栗山進一, 栗山進一, 栗山進一, 寳澤篤, 寳澤篤, 大隅典子, 大隅典子, 清元秀泰, 清元秀泰, 菅原準一, 菅原準一, 鈴木洋一, 鈴木洋一, 冨永悌二, 冨永悌二, 布施昇男, 布施昇男, 峯岸直子, 峯岸直子, 辻一郎, 辻一郎, 呉繁夫, 呉繁夫, 八重樫伸生, 八重樫伸生, 山本雅之, 山本雅之

    Journal of Epidemiology (Web)　26　(Supplement 1)　105　2016/01/21

    ISSN： 1349-9092

  36. 東日本大震災後の宮城県におけるメタボリック症候群の規定要因:地域住民コホート調査

    中村智洋, 中谷直樹, 土屋菜歩, 成田暁, 丹野高三, 佐々木亮平, 坂田清美, 高井貴子, 荻島創一, 峯岸直子, 清元秀泰, 鈴木洋一, 菅原準一, 布施昇男, 菊谷昌浩, 栗山進一, 辻一郎, 呉繁夫, 寳澤篤

    Journal of Epidemiology (Web)　26　(Supplement 1)　124　2016/01/21

    ISSN： 1349-9092

  37. 東日本大震災後の宮城県におけるメタボリック症候群の規定要因:地域住民コホート調査

    中村智洋, 中谷直樹, 土屋菜歩, 成田暁, 丹野高三, 佐々木亮平, 坂田清美, 高井貴子, 荻島創一, 峯岸直子, 清元秀泰, 鈴木洋一, 菅原準一, 布施昇男, 菊谷昌浩, 栗山進一, 辻一郎, 呉繁夫, 寳澤篤

    Journal of Epidemiology (Web)　26　(Supplement 1)　124　2016/01/21

    ISSN： 0917-5040

  38. 随時尿Na/K比,随時尿からの推定食塩摂取量と血圧値の相関について―東北メディカル・メガバンク事業―

    寳澤篤, 清元秀泰, 中谷直樹, 中村智洋, 土屋菜歩, 成田暁, 小暮真奈, 菅原準一, 布施昇男, 菊谷昌浩, 鈴木洋一, 荻島創一, 高井貴子, 峯岸直子, 栗山進一, 辻一郎, 呉繁夫, 丹野高三, 佐々木亮平, 坂田清美

    Journal of Epidemiology (Web)　26　(Supplement 1)　123　2016/01/21

    ISSN： 1349-9092

  39. 随時尿Na/K比,随時尿からの推定食塩摂取量と血圧値の相関について―東北メディカル・メガバンク事業―

    寳澤篤, 清元秀泰, 中谷直樹, 中村智洋, 土屋菜歩, 成田暁, 小暮真奈, 菅原準一, 布施昇男, 菊谷昌浩, 鈴木洋一, 荻島創一, 高井貴子, 峯岸直子, 栗山進一, 辻一郎, 呉繁夫, 丹野高三, 佐々木亮平, 坂田清美

    Journal of Epidemiology (Web)　26　(Supplement 1)　123　2016/01/21

    ISSN： 0917-5040

  40. マタニティログ調査:ヘルスケアデータと多層オミックスデータによる妊娠関連疾患の予防・早期発見に向けたコホート調査

    原田祐希, 越智大介, 山内隆史, 山下理宇, 高井貴子, 荻島創一, 峯岸直子, 田邉修, 田邉修, 栗山進一, 栗山進一, 布施昇男, 八重樫伸生, 八重樫伸生, 山本雅之, 山本雅之, 檜山聡, 長崎正朗, 菅原準一, 菅原準一

    日本分子生物学会年会プログラム・要旨集(Web)　39th　ROMBUNNO.3LBA‐096 (WEB ONLY)　2016

  41. 日本人全ゲノムファレンスパネルの構築と今後

    日本遺伝学会大会プログラム・予稿集　87th　73　2015/09

  42. 東北メディカル・メガバンク事業-地域住民コホート調査のデザインと経過報告(眼圧検査)

    布施 昇男, 本間 慶, 高井 貴子, 清元 秀泰, 菅原 準一, 鈴木 洋一, 菊谷 昌浩, 栗山 進一, 寳澤 篤, 八重樫 伸生, 山本 雅之

    日本緑内障学会抄録集　26回　(Supplement 1)　130-130　2015/09

    Publisher: 日本緑内障学会

    ISSN： 0917-5040

  43. Preperimetric glaucoma pathophysiological study part3: Association between EDNRA genotype and the effect of a prostaglandin analogue on ocular blood flow

    Yukihiro Shiga, Nobuo Fuse, Kota Sato, Naoko Aizawa, Satoru Tsuda, Masae Kimura, Koji Nishiguchi, Tomoki Yasui, Keiichi Kato, Toru Nakazawa

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　56　(7)　2015/06

    ISSN： 0146-0404

    eISSN： 1552-5783

  44. 東北メディカル・メガバンク 地域住民コホート宮城エリアにおける随時尿Na/K比の内陸部・沿岸部比較

    寳澤 篤, 中谷 直樹, 中村 智洋, 土屋 菜歩, 小暮 真奈, 丹野 高三, 佐々木 亮平, 坂田 清美, 中谷 純, 峯岸 直子, 清元 秀泰, 菅原 準一, 布施 昇男, 菊谷 昌浩, 鈴木 洋一, 富田 博秋, 栗山 進一, 辻 一郎, 呉 繁夫, 八重樫 伸生, 山本 雅之

    日本循環器病予防学会誌　50　(2)　126-126　2015/06

    Publisher: (一社)日本循環器病予防学会

    ISSN： 1346-6267

  45. 眼疾患の遺伝子診断の実情(商業ゲノムデータベースを含む)

    布施 昇男

    眼科　56　(13)　1533-1543　2014/12

    Publisher: 金原出版

    ISSN： 0016-4488

  46. 被災地健康調査における家庭血圧計診断に基づく高血圧症の実態

    清元 秀泰, 寳澤 篤, 田中 由香利, 奥田 拓史, 菅原 準一, 坪井 明人, 布施 昇男, 栗山 進一, 瀧 靖之, 辻 一郎, 阿部 倫明, 高井 貴子, 八重樫 伸生, 山本 雅之, 伊藤 貞嘉

    日本高血圧学会総会プログラム・抄録集　37回　442-442　2014/10

    Publisher: (NPO)日本高血圧学会

  47. 緑内障 (特集 眼と遺伝)

    布施 昇男

    眼科　56　(5)　599-607　2014/04

    Publisher: 金原出版

    ISSN： 0016-4488

  48. 眼疾患と遺伝子 緑内障のゲノム解析 次世代医療・個別化医療に向けて

    布施 昇男, 清水 愛, 木村 雅恵, 高野 良真, 石 棟, 宮澤 晃子, 国松 志保, 劉 孟林, 渡邉 亮, 安田 正幸, 横山 悠, 檜森 紀子, 津田 聡, 山本 耕太郎, 中澤 徹, 安田 純, 勝岡 史城, 小島 要, 成相 直樹, 松本 光代, 元池 育子, 長崎 正朗, 木下 賢吾, 五十嵐 和彦, 山本 雅之, 新堀 哲也, 青木 洋子, 松原 洋一, 舟山 亮, 長嶋 剛史, 中山 啓子, 眞島 行彦, 船山 智代, 田中 光一, 原田 高幸, 阿部 春樹, 福地 健郎, 安田 典子, 出田 秀尚, 鄭 暁東, 白石 敦, 大橋 裕一, 石田 誠夫, 原 岳, 金森 章泰, 山田 裕子, 中村 誠, 酒井 寛, Richards Julia E

    日本眼科学会雑誌　118　(3)　216-240　2014/03

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  49. 東北メディカル・メガバンク事業―地域住民コホート調査に関する経過報告

    寶澤篤, 寶澤篤, 寶澤篤, 中谷直樹, 中村智洋, 土屋菜歩, 菊谷昌浩, 目時弘仁, 小原拓, 大隅典子, 清元秀泰, 菅原準一, 鈴木洋一, 中谷直樹, 中村智洋, 土屋菜歩, 菊谷昌浩, 目時弘仁, 小原拓, 大隅典子, 清元秀泰, 菅原準一, 鈴木洋一, 富田博秋, 富田博秋, 富田博秋, 冨永悌二, 中谷純, 布施昇男, 峯岸直子, 辻一郎, 八重樫伸生, 山本雅之, 冨永悌二, 中谷純, 布施昇男, 峯岸直子, 辻一郎, 八重樫伸生, 山本雅之

    J Epidemiol　24　(Supplement 1)　67　2014/01/23

    ISSN： 0917-5040

  50. 東北メディカル・メガバンク事業―三世代コホート調査に関する経過報告

    目時弘仁, 小原拓, 石黒真美, 成川洋子, 菊谷昌浩, 目時弘仁, 小原拓, 石黒真美, 成川洋子, 菊谷昌浩, 栗山進一, 栗山進一, 栗山進一, 中谷直樹, 寶澤篤, 大隅典子, 清元秀泰, 菅原準一, 鈴木洋一, 中谷直樹, 寶澤篤, 大隅典子, 清元秀泰, 菅原準一, 鈴木洋一, 富田博秋, 富田博秋, 富田博秋, 冨永悌二, 中谷純, 布施昇男, 峯岸直子, 辻一郎, 八重樫伸生, 冨永悌二, 中谷純, 布施昇男, 峯岸直子, 辻一郎, 八重樫伸生

    J Epidemiol　24　(Supplement 1)　67　2014/01/23

    ISSN： 0917-5040

  51. 緑内障 (特集 ゲノムと網膜関連疾患の関与を探る)

    布施 昇男

    Retina medicine : journal of retina medeicine : 網膜・硝子体領域を中心とした医学情報誌　3　(1)　50-55,9　2014

    Publisher: 先端医学社

    ISSN： 2187-2384

  52. 東北メディカル・メガバンク事業 三世代コホート調査の進捗について

    目時 弘仁, 石黒 真美, 小原 拓, 佐藤 ゆき, 菊谷 昌浩, 栗山 進一, 寳澤 篤, 大隅 典子, 清元 秀泰, 菅原 準一, 鈴木 洋一, 冨永 悌二, 布施 昇男, 峯岸 直子, 辻 一郎, 呉 繁夫, 八重樫 伸生, 山本 雅之

    DOHaD研究　3　(1)　46-46　2014

    Publisher: 日本DOHaD研究会

    ISSN： 2187-2597

    More details Close

    第3回日本DOHaD研究会学術集会 抄録集 【ポスター発表】

  53. 次世代シークエンサーを用いた新規発達緑内障遺伝子の探索

    清水愛, 新堀哲也, 青木洋子, 松原洋一, 舟山亮, 長嶋剛史, 中山啓子, 渡邉亮, 長崎正朗, 布施昇男, 中澤徹

    日本眼科学会雑誌　117　2013

    ISSN： 0029-0203

  54. Guidelines for Glaucoma Tube-shunt Surgery

    116　(4)　388-393　2012/04/10

    Publisher: 日本眼科学会

    ISSN： 0029-0203

  55. Authors' reply

    Hiroshi Kunikata, Toshiaki Abe, Nobuo Fuse, Toru Nakazawa

    Ophthalmic Surgery Lasers and Imaging　43　(2)　175　2012/03

    DOI： 10.3928/15428877-20120206-01 　

    ISSN： 1542-8877

  56. The Management of Dislocated Intraocular Lenses Reply

    Hiroshi Kunikata, Toshiaki Abe, Nobuo Fuse, Toru Nakazawa

    OPHTHALMIC SURGERY LASERS & IMAGING　43　(2)　175-175　2012/03

    ISSN： 1542-8877

  57. 眼球鉄錆症による続発緑内障の1例

    野口 三太朗, 渡邉 亮, 布施 昇男, 馬場 耕一, 阿部 圭子, 山田 孝彦, 高橋 秀肇, 中澤 徹

    あたらしい眼科　29　(3)　419-423　2012/03

    Publisher: (株)メディカル葵出版

    ISSN： 0910-1810

  58. 緑内障眼における黄斑部網膜神経節細胞複合体とHumphrey視野検査30-2中心8点との相関

    臨床眼科　66　(9)　1319-1323　2012

  59. 大きな硝子体内異物に対する25G手術による無縫合異物摘出術

    國方彦志, 植松恵, 布施昇男, 中澤徹

    眼科手術　25　42　2011/12/28

    ISSN： 0914-6806

  60. Polymorphisms in ARMS2 (LOC387715) and LOXL1 Genes in the Japanese With Age-Related Macular Degeneration REPLY

    Nobuo Fuse, Toshiaki Abe, Kohji Nishida

    AMERICAN JOURNAL OF OPHTHALMOLOGY　152　(3)　499-500　2011/09

    ISSN： 0002-9394

  61. 全身虚血性疾患合併の緑内障における皮膚AGE測定の有用性

    金澤 紘子, 安田 正幸, 志村 雅彦, 布施 昇男, 宮田 敏男, 中澤 徹

    日本緑内障学会抄録集　22回　101-101　2011/09

    Publisher: 日本緑内障学会

  62. Polymorphisms in ARMS2 (LOC387715) and LOXL1 Genes in the Japanese With Age-Related Macular Degeneration REPLY

    Nobuo Fuse, Toshiaki Abe, Kohji Nishida

    AMERICAN JOURNAL OF OPHTHALMOLOGY　152　(2)　326-326　2011/08

    ISSN： 0002-9394

  63. Recurrence of uveal effusion in a case twenty-three years after initial sclerectomy

    岡村知世子, 國方彦志, 阿部俊明, 中澤満, 布施昇男

    臨床眼科　65　(6)　895-900　2011/06/15

    Publisher: 医学書院

    DOI： 10.11477/mf.1410103699 　

    ISSN： 0370-5579

    eISSN： 1882-1308

  64. Changes in axial length in children measured by noncontact laser interference biometry

    65　(6)　817-820　2011/06

    Publisher: 医学書院

    ISSN： 0370-5579

  65. Medium-Term Efficacy and Safety of Infliximab in Behcet's Disease with Refractory Uveitis

    OKAMURA Chiyoko, OTOMO Takaaki, FUSE Nobuo, ABE Toshiaki

    Journal of the eye　28　(5)　696-701　2011/05/30

    Publisher: メディカル葵出版

    ISSN： 0910-1810

  66. 糖尿病黄斑浮腫眼における前房水サイトカインケモカインの解析

    國方彦志, 志村雅彦, 中澤徹, 園田康平, 吉村武, 石橋達郎, 西田幸二, 布施昇男

    日本眼科学会雑誌　115　(臨増)　232-232　2011/04/15

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  67. 当院における増殖性糖尿病網膜症の悪化因子の検討

    鬼怒川 次郎, 國方 彦志, 阿部 俊明, 新田 文彦, 安田 正幸, 布施 昇男

    日本眼科学会雑誌　115　(臨増)　301-301　2011/04

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  68. Role of glutamate transporters in glaucoma

    Michiko Yanagisawa, Sayaka Kato, Takuya Takeda, Tomomi Aida, Takayuki Harada, Nobuo Fuse, Kohichi Tanaka

    NEUROSCIENCE RESEARCH　71　E200-E200　2011

    DOI： 10.1016/j.neures.2011.07.864 　

    ISSN： 0168-0102

  69. 緑内障における Genome-Wide Association Study

    布施 昇男

    あたらしい眼科 = Journal of the eye　26　(11)　1503-1504　2009/11/30

    ISSN： 0910-1810

  70. Primary open angle glaucoma (in the narrow sense)

    51　(5)　597-611　2009/05

    Publisher: 金原出版

    ISSN： 0016-4488

  71. New Insights into Secondary Glaucoma-Related Genes

    FUSE Nobuo

    Journal of the eye　26　(3)　285-293　2009/03/30

    Publisher: メディカル葵出版

    ISSN： 0910-1810

  72. 遺伝解析の現状 (緑内障診療--グレーゾーンを越えて) -- (診断編 疫学調査と遺伝)

    布施 昇男

    臨床眼科　63　(11)　200-209　2009

    Publisher: 医学書院

    ISSN： 0370-5579

  73. 落屑症候群・落屑緑内障の原因遺伝子LOXL1遺伝子

    布施 昇男, 山下 英俊

    あたらしい眼科 = Journal of the eye　25　(10)　1399-1400　2008/10/30

    Publisher: メディカル葵出版

    ISSN： 0910-1810

  74. Correlation between visual field defect and retinal nerve fiber layer thickness in glaucoma

    62　(5)　723-726　2008/05

    Publisher: 医学書院

    ISSN： 0370-5579

  75. 緑内障の遺伝子研究の最新情報は? (緑内障Now!) -- (緑内障研究の最新情報)

    布施 昇男

    あたらしい眼科　25　203-206　2008

    Publisher: メディカル葵出版

    ISSN： 0910-1810

  76. A case of lacrimal gland pleomorphic adenoma

    49　(6)　849-854　2007/06

    Publisher: 金原出版

    ISSN： 0016-4488

  77. ICG,TB色素の低温下暴露における培養網膜色素上皮細胞に対する毒性

    國方彦志, 阿部俊明, 村田裕美, 相良淑子, 涌沢亮介, 吉田光, 吉田まどか, 布施昇男

    眼科臨床医報　100　(10)　808-808　2006/10/15

    Publisher: 眼科臨床医報会

    ISSN： 0386-9601

  78. 080 緑内障に対する鍼治療の検討(鍼灸4,一般演題,第57回日本東洋医学会学術総会)

    関隆志, 来須正幸, 相良淑子, 布施昇男, 岩崎鋼, 藤原博典, 古川勝敏, 荒井啓行, 佐々木英忠

    日本東洋醫學雜誌　57　205-205　2006/05/31

    Publisher: 社団法人日本東洋医学会

    ISSN： 0287-4857

  79. 緑内障に対する鍼治療の検討 (日本東洋医学雑誌)

    関隆志, 来須正幸, 相良淑子, 布施昇男, 岩崎鋼, 藤原博典, 古川勝敏, 荒井啓行, 佐々木英忠

    日本東洋医学雑誌　57　(別冊)　205-205　2006/05

  80. 緑内障患者に対する鍼灸治療のQOLの改善効果の検討 (日本老年医学会雑誌)

    関隆志, 布施昇男, 岩崎鋼, 荒井啓行, 佐々木英忠

    日本老年医学会雑誌　43　(Suppl.)　131-131　2006/05

  81. ICG色素の低温下暴露における培養網膜色素上皮細胞に対する毒性

    国方彦志, 富田浩史, 阿部俊明, 村田裕美, 相良淑子, 佐藤肇, 和田裕子, 布施昇男, 玉井信, 西田幸二

    日本眼科学会雑誌　110　(臨増)　204-204　2006/03/15

    Publisher: (公財)日本眼科学会

    ISSN： 0029-0203

  82. 緑内障に対する針刺激の検討 (日本老年医学会雑誌)

    関隆志, 来須正幸, 布施昇男, 岩崎鋼, 荒井啓行, 佐々木英忠

    日本老年医学会雑誌　43　(2)　255-255　2006/03

  83. 緑内障に対する鍼灸治療の検討 (日本老年医学会雑誌)

    関隆志, 来須正幸, 相良淑子, 布施昇男, 岩崎鋼, 荒井啓行, 佐々木英忠

    日本老年医学会雑誌　42　(Suppl.)　77-77　2005/05

  84. Pattern Reversal VEP and contrast sensitive accurate test after acupuncture stimulation in glaucoma subjects

    Y Sagara, N Fuse, T Nakazawa, K Watanabe, H Akiyama, M Seimiya, S Yokokura, M Kurusu, T Seki, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　46　2005

    ISSN： 0146-0404

  85. Application of Acupuncture in Ophthalmology

    WATANABE Kei, NAKAZAWA Toru, SAGARA Yoshiko, FUSE Nobuo, TAKAHASHI Kana, AKIYAMA Hiroshi, SEIMIYA Motohiko, NAKAMURA Masahiko, SEKI Takashi, KURUSU Masayuki, SHIMURA Masahiko, TAMAI Makoto

    14　(1)　71-74　2004/09/20

    ISSN： 0917-4338

  86. Latanoprost prevents retinal ganglion cell death induced by N-methyl-D-aspartate or optic nerve axotomy

    H Kudo, T Nakazawa, K Kashiwagi, M Shimura, H Takahashi, N Fuse, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　45　U355-U355　2004/04

    ISSN： 0146-0404

  87. Pitavastatin protects against retinal ganglion cell damage injured by intravitreous application of N-methyl-D-aspartate and optic nerve axotomy

    H Takahashi, T Nakazawa, M Shimura, K Yasuda, N Fuse, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　45　U358-U358　2004/04

    ISSN： 0146-0404

  88. P-VEP (pattern reversal visual evoked potentials) to identify the improvements of visual functions by acupuncture stimuli

    Y Sagara, K Watanabe, T Nakazawa, N Fuse, K Takahashi, H Akiyama, M Seimiya, T Seki, M Kurusu, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　45　U660-U660　2004/04

    ISSN： 0146-0404

  89. Intravitreal administration of N-methyl-D-aspartate (NMDA) induces cell death both in the ganglion and arracrine cells with the suppression ofprotein kinase B (Akt) activity.

    T Nakazawa, M Shimura, S Endo, N Fuse, H Takahashi, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　45　U354-U354　2004/04

    ISSN： 0146-0404

  90. Evaluation of human deleted in polyposis 1-like 1 as a candidate glaucoma gene

    N Fuse, H Sato, M Seimiya, T Nakazawa, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　45　U439-U439　2004/04

    ISSN： 0146-0404

  91. Application of Acupuncture in Ophthalmology

    WATANABE Kei, NAKAZAWA Toru, SAGARA Yoshiko, FUSE Nobuo, TAKAHASHI Kana, AKIYAMA Hiroshi, SEIMIYA Motohiko, NAKAMURA Masahiko, SEKI Takashi, KURUSU Masayuki, SHIMURA Masahiko, TAMAI Makoto

    Journal of the eye　21　(3)　393-396　2004/03/30

    Publisher: メディカル葵出版

    ISSN： 0910-1810

  92. Evaluation of Nitric Oxide Synthase 3 (NOS3) as a candidate glaucoma gene

    N Fuse, CM Krafchak, CA Downs, SE Moroi, PR Lichter, JE Richards

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　43　U963-U963　2002/05

    ISSN： 0146-0404

  93. Clinical variability of patients associated with gene mutations of visual cycle protein, arrestin, RPE65 and RDH5 genes

    Y Wada, M Nakazawa, T Abe, N Fuse, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　41　(4)　S617-S617　2000/03

    ISSN： 0146-0404

  94. The structure and function of nicrophthalmia-associated transcription factor, MITF

    YASUMOTO Ken-ichi, UDONO Tetsuo, WATANABE Ken-ichi, SAITO Hideo, AMAE Shintaro, FUSE Nobuo, TAKEDA Kazuhisa, SHIBAHARA Shigeki

    日本分子生物学会年会プログラム・講演要旨集　21　420-420　1998/12/01

  95. Identification of a melanocyte-type promoter of the microphthalmia-associated transcription factor gene

    N Fuse, K Yasumoto, H Suzuki, K Takahashi, S Shibahara, M Tamai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE　38　(4)　5295-5295　1997/03

    ISSN： 0146-0404

  96. 色素細胞特異的な遺伝子発現に関与する転写因子MITFの機能解析

    安元 研一, 布施 昇男, 柴原 茂樹

    日本分子生物学会年会プログラム・講演要旨集　19　601-601　1996/08/01

Show all ︎Show first 5

Books and Other Publications 25

  1. New trends in genetic statistics

    2024/03

  2. All About Primary Open Angle Glaucoma

    Nobuo Fuse

    2022/04

  3. すぐに役立つ眼科日常診療のポイント

    布施 昇男

    全日本病院出版会　2018/10

  4. 多因子遺伝性疾患研究と遺伝カウンセリング

    櫻井晃洋, 布施昇男

    メディカルドュ　2018/06

  5. ヒト疾患のデータベースとバイオバンク

    山本雅之, 荻島創一, 布施昇男

    羊土社　2017/11

  6. 目

    こどもくらぶ, 布施, 昇男, 稲葉, 茂勝

    ベースボール・マガジン社　2017/03

    ISBN: 9784583110097

  7. 前視野緑内障に向き合う

    布施 昇男

    文光堂　2016/10

  8. 実戦眼科薬理

    布施 昇男

    医学書院　2013/11

  9. 眼手術学

    布施 昇男

    文光堂　2012/02

  10. 全身疾患と眼

    村田敏規, 布施昇男

    中山書店　2011/06

  11. 緑内障診断ガイド

    相原一, ed, 布施昇男

    中山書店　2011/01

  12. 動画でわかる緑内障手術

    谷原秀信, 布施昇男

    中山書店　2010/04

  13. 動画でわかる緑内障手術

    Nobuo Fuse

    中山書店　2010/03

  14. 疫学調査と遺伝. 遺伝解析の現状

    布施 昇男

    医学書院　2009/11

  15. 内障の遺伝要因（内的因子）と環境因子（外的因子）原発開放隅角緑内障

    布施 昇男

    金原出版　2009/05

  16. 眼科プラクティス 眼科レーザー治療

    Nobuo Fuse

    文光堂　2009/04

  17. 眼科レーザー治療

    田野保雄, 布施昇男

    文光堂　2009/03/24

  18. 続発緑内障に関連した遺伝子はここまでわかった（あたらしい眼科）

    布施 昇男

    メディカル葵出版社　2009/03

  19. 緑内障の遺伝子研究の最新情報は？（あたらしい眼科）

    布施 昇男

    メディカル葵出版社　2008/10

  20. 眼科医のための先端医療、落屑症候群・落屑緑内障の原因遺伝子LOXL1遺伝子（あたらしい眼科）

    布施 昇男

    メディカル葵出版社　2008/10

  21. 眼科診療のスキルアップ緑内障編

    谷原秀信, 布施昇男

    メディカルビュー社　2008/10/01

  22. 眼科開業医のための疑問・難問解決策

    後藤浩, 山田昌和, 吉川啓司, 飯野倫子, 布施昇男

    診断と治療社　2006/10

  23. 臨床眼科・手術のタイミングとポイント

    西田輝夫, 布施昇男

    医学書院　2006/10

  24. 緑内障3分診療を科学する

    吉川啓司, 松元俊, ed, 布施昇男

    中山書店　2006/09

  25. 眼科プラクティス、緑内障診療の進め方

    根木昭, ed, 布施昇男

    文光堂　2006/09

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Presentations 128

  1. コホート調査における眼圧測定とゲノムワイド相関解析

    布施昇男

    第227回宮城県眼科集談会　2026/01/17

  2. ゲノム・オミックス情報の活用による 個別化医療の基盤形成に向けて Invited

    布施昇男

    東京都立大学多視座涵養講座　2025/10/24

  3. Genome-wide association study of optic disc parameters

    2025/09/13

  4. Genome and personalized medicine Invited

    2024/11/13

  5. Profiles of pathogenic variant carriers of Lynch syndrome found in a population-based research biobank participants

    Kinuko Ohneda, Masanobu Takahashi, Yoichi Suzuki, Yohei Hamanaka, Junko Minato, Muneaki Shimada, Yumi Yamaguchi-Kabata, Shu Tadaka, Kengo Kinoshita, Hiroshi Kawame, Fuji Nagami, Nobuo Fuse, Masayuki Yamamoto

    2024/10/12

  6. Clinical outcome of returning genomic results to BRCA1 and BRCA2 pathogenic variant carriers found in general population

    Yoichi Suzuki, Kinuko Ohneda, Yohei Hamanaka, Takanori Ishida, Junko Minato, Muneaki Shimada, Hiroshi Kawame, Nobuo Fuse, Fuji Nagami, Masayuki Yamamoto

    2024/10/10

  7. Investigating the Genetic Correlates of Optic Disc Parameters in the ToMMo Eye Study

    Makiko Taira, Takanori Hidaka, Tomo Saito, Fuji Nagami, Kengo Kinoshita, Masayuki Yamamoto, Nobuo Fuse

    2024/10/10

  8. 嗅覚、認知機能検査データと脳灰白質容積の関連性検討

    佐藤守一, 今枝孝夫, 麦倉俊司, 森菜緒子, 高梨昌樹, 早川和美, 長神 風二, 布施昇男, 荻島創一, 中村智洋, 齊藤智, 栗山進一, 寳澤篤

    第13回日本認知症予防学会学術集会　2024/09/28

  9. GWAS of intraocular pressure in the health survey

    2024/09/20

  10. 一般住民健康調査が教えてくれるもの Invited

    布施昇男

    第90回埼玉眼科講習会　2024/07/26

  11. ゲノムワイド関連解析による近視の発症に関わる遺伝子同定 Invited

    布施昇男

    第６回日本近視学会総会　2024/05/18

  12. 東北メディカル・メガバンク計画健康調査における中心角膜厚のゲノムワイド関連解析

    布施昇男, 安澤 隼人, 元池育子, 櫻井美由紀, 木下賢吾, 山本雅之

    第128回日本眼科学会総会　2024/04/18

  13. 地域住民コホート研究における屈折異常の有病率および関連する因子の解析

    布施 昇男

    第221回宮城県眼科集談会　2024/01/20

  14. 予測医学とゲノム技術の融合による精密医療に向けて Invited

    布施昇男

    第76回日本胸部外科学会定期学術集会　2023/10/20

  15. Realizing precision medicine by utilizing genomic information Invited

    Nobuo Fuse

    The 77th Annual Congress of Japan Clinical Ophthalmology　2023/10/09

  16. 地域住民コホート研究における屈折異常の有病率および関連する因子の解析

    布施 昇男, 三木 篤也, 藤本 聡子, 平良 摩紀子, 齊藤 智, 岡崎 智之, 白木 彰彦, 佐藤 茂, 川崎 良, 中村 智彦, 木下 賢吾, 西田幸二, 山本雅之

    第77回臨床眼科学会　2023/10/08

  17. 東北メディカル・メガバンク計画健康調査における眼軸長のゲノムワイド関連解析

    布施昇男, 櫻井美由紀, 元池育子, 小島要, 平良摩紀子, 宇留野晃, 濵中洋平, 中村智洋, 荻島創一, 寳澤篤, 栗山進一, 呉繁夫, 木下賢吾, 山本雅之

    日本眼科学会　2022/04/15

  18. Genetics of POAG Invited

    2020/10/02

  19. The Tohoku Medical Megabank Project to Realize Personalized Medicine International-presentation Invited

    FUSE Nobuo

    Japan-NIH-JSPS Joint Symposium　2019/10/29

  20. Next generation sequencing and genome-wide data analysis for glaucoma International-presentation Invited

    FUSE Nobuo

    NHRI 2018 Precision Medicine, Technology and Development Symposium　2018/10/06

  21. 身近になったゲノム医療 東北メディカル・メガバンク計画の目標と進捗状況‐世界最先端のバイオバンク構築を目指して‐

    布施 昇男

    第153回日本医学会シンポジウム　2018/06/20

  22. 1070 人全ゲノム解析から見えた眼科疾患 （AR） の保因者頻度； 特に網膜色素変性 Invited

    布施 昇男

    第70回臨床眼科学会　2016/11/03

  23. Genome cohort study and association study for axial length and refractive error in Japanese. International-presentation

    FUSE Nobuo

    International Society for Eye Research　2016/09/29

  24. Updates on Genetic Epidemiology in Ophthalmology: Genome Cohort Study. International-presentation

    FUSE Nobuo

    Asia-ARVO　2015/02/17

  25. Genetics, Autophagy, and Glaucoma: Whole exome sequencing and autophagy candidate gene. International-presentation

    FUSE Nobuo

    World Ophthalmology Congress (WOC).　2014/04/03

  26. Association between optic nerve microcirculation and glaucomatous damage. International-presentation

    FUSE Nobuo

    5th World Glaucoma Congress　2013/07/19

  27. ゲノム情報でつくる新しい医療

    布施昇男

    東北メディカルメガバンク機構コホート事業 キックオフシンポジウム　2013/04/20

  28. Genome Analysis for Glaucoma – For personalized medicine in future – Invited

    2013/04/06

  29. Molecular Genetic Analysis for Glaucoma using Next-Generation Sequencing Technology

    FUSE Nobuo

    Asia-Pacific Academy of Ophthalmology　2013/01/18

  30. Genetics and Biomarkers in Glaucoma International-presentation

    FUSE Nobuo

    2012/04/14

  31. 落下IOL、偏位IOLの小切開アプローチ

    國方彦志, 布施昇男, 阿部俊明

    第182回宮城県眼科集談会　2011/01/22

  32. 緑内障・手術療法Review

    布施昇男

    12回Japan Glaucoma Council　2010/12/11

  33. 緑内障治療の選択肢について

    布施昇男

    アルコンオフサルミックセミナー　2010/11/27

  34. 緑内障薬物治療の選択肢について

    布施昇男

    第一回 福島臨床眼科講演会　2010/11/20

  35. OCTによる網膜神経線維層厚測定の緑内障経過観察における有用性

    千葉真生, 中澤徹, 面高宗子, 布施昇男

    第64回臨床眼科学会　2010/11/11

  36. 緑内障の診断とテーラーメード治療

    布施昇男

    ザラカム発売記念講演会　2010/10/27

  37. これからの薬物治療

    布施昇男

    第15回みやぎ薬剤師学術研修会　2010/10/23

  38. 緑内障診断のための眼底読影のポイント

    布施昇男

    宮城沿岸眼底読影勉強会　2010/10/16

  39. 眼科疾患、治療のトピックス

    布施昇男

    平成２２年度宮城県医師会医師研修講習会　2010/10/14

  40. 線維柱帯切除術の術後合併症

    布施昇男

    第９回五国緑内障round table discussion　2010/08/21

  41. 緑内障はどんな病気？

    布施昇男

    目の健康講座　2010/07/24

  42. これからの緑内障薬物治療

    布施昇男

    白河地区勉強会　2010/06/11

  43. 緑内障手術適応と合併症

    布施昇男

    先端医療勉強会 in 横浜　2010/05/14

  44. Superior segmental optic hypoplasiaの網膜神経線維層厚の解析

    布施昇男, 中澤徹, 佐渡一成, 面高宗子, 中村政彦, 西田幸二

    第114回日本眼科学会　2010/04/15

  45. Laser Speckle Flowgraphyによる眼底血流の検討

    相澤奈帆子, 中澤徹, 布施昇男, 西田幸二

    第114回日本眼科学会　2010/04/15

  46. 緑内障診断の眼底読影のポイントと視野の読み方

    布施昇男

    鹿児島緑内障勉強会　2010/04/10

  47. 眼底読影のポイントと視野の読み方

    布施昇男

    八戸眼底読影勉強会　2010/03/13

  48. 眼底読影のポイントと視野の読み方

    布施昇男

    福島ひまわり会眼底読影勉強会　2009/12/07

  49. 緑内障手術

    布施昇男

    みやぎ眼科臨床座談会　2009/12/04

  50. 眼底読影のポイントと視野の読み方

    布施昇男

    函館眼底読影勉強会　2009/11/27

  51. 緑内障の手術適応について

    布施昇男

    仙南緑内障講演会　2009/11/21

  52. 線維柱帯切除術が角膜高次収差に与える影響

    布施昇男, 大家義則, 中澤徹, 雪田昌克, 西田幸二

    第19回緑内障学会　2009/11/13

  53. 緑内障治療の考え方

    布施昇男

    第20回日本緑内障学会　2009/11/13

  54. 高眼圧眼における眼圧降下治療の眼循環への影響

    中澤 徹, 布施昇男, 面高宗子, 相澤奈帆子, 西田幸二

    第20回日本緑内障学会　2009/11/13

  55. 開放隅角緑内障におけるOCTを用いた乳頭周囲網膜神経線維層厚と視機能との部位別相関

    面高 宗子, 中澤 徹, 布施 昇男, 西田 幸二

    第20回日本緑内障学会　2009/11/13

  56. レーザースッペクル眼底血流画像化法の再現性

    相澤奈帆子, 中澤 徹, 布施昇男, 劉 猛林, 檜森紀子, 面高宗子, 西田幸二

    第20回日本緑内障学会　2009/11/13

  57. 緑内障性視神経症(GON)に対する分子遺伝学の切れ味

    布施昇男

    第30回西中国眼疾患フォーラム　2009/10/29

  58. Evaluation of external trabeculotomy and trabeculectomy for treatment of steroid-induced glaucoma International-presentation

    Nobuo Fuse, Toru Nakazawa, Kohji Nishida

    American Academy of Ophthalmology　2009/10/24

  59. 東北大学におけるトラバタンズ点眼液の使用経験

    布施昇男

    東北臨床眼科セミナー　2009/10/17

  60. ステロイド緑内障に対する初回トラベクロトミー、トラベクレクトミーの効果

    布施昇男, 中澤徹, 真壁春菜, 太田有夕美, 西田幸二

    第63回日本臨床眼科学会　2009/10/09

  61. 緑内障診断における眼底読影の重要性

    布施昇男

    第12回川崎市眼疾患研究会　2009/07/11

  62. 緑内障手術と治療

    布施昇男

    仙石の会　2009/06/06

  63. 緑内障手術の行方

    布施昇男

    一関学術講演会　2009/05/09

  64. 緑内障手術適応の悩み

    布施昇男

    札幌学術講演会　2009/04/25

  65. 開放隅角緑内障の原因遺伝子

    布施昇男

    第113回日本眼科学会　2009/04/16

  66. 加齢黄斑変性におけるLOXL1遺伝子の解析

    宮澤晃子, 布施昇男, 中澤徹, 涌沢亮介, 阿部俊明, 西田幸二

    第113回日本眼科学会　2009/04/16

  67. 東北大学における進行緑内障の病型と視神経乳頭形状の特徴

    中澤 徹, 布施昇男, 面高 宗子, 宮澤 晃子, 工藤 英代, 横山 悠, 大友 孝昭, 西田 幸二

    第113回日本眼科学会　2009/04/16

  68. 開放隅角緑内障のHRTを用いた乳頭画像解析における乳頭形状分類の有用性

    面高 宗子, 中澤 徹, 布施 昇男, 宮澤 晃子, 工藤 英代, 土井 洋, 大友 孝昭, 西田 幸二

    第113回日本眼科学会　2009/04/16

  69. ステロイド緑内障

    布施昇男

    第9回角膜緑内障研究会　2009/03/27

  70. 緑内障治療における手術の位置づけ

    布施昇男

    第27回郡山眼科おはなし会　2009/02/27

  71. 緑内障手術適応の悩み

    布施昇男

    第8回Sunday Glaucoma Meeting　2009/02/08

  72. この症例に手術するか

    布施昇男

    第1回岡山緑内障ラウンドミーティング　2008/11/22

  73. 緑内障の病態と分子遺伝学的解析

    布施昇男

    第368回東北医学会例会シンポジウム　2008/11/14

  74. これからの緑内障遺伝子研究の展望

    布施昇男

    緑内障若手研究者の会　2008/10/24

  75. GHTのグレイゾーン

    布施昇男

    第62回臨床眼科学会　2008/10/23

  76. 落屑緑内障における線維柱帯切開術と線維柱帯切除術の術後成績

    布施昇男, 大友孝昭, 宮澤晃子, 中澤 徹, 横山 悠, 清宮基彦, 西田幸二

    第62回臨床眼科学会　2008/10/23

  77. 正常眼圧緑内障の視神経乳頭形状とＭＤslopeの相関

    中澤徹, 布施昇男, 横山悠, 大友孝昭, 清宮基彦, 西田幸二

    第62回臨床眼科学会　2008/10/23

  78. 若年者の解放隅角緑内障の診断とフォローについて

    布施昇男

    滋賀県眼科セミナー　2008/09/27

  79. 緑内障の病態別治療

    布施昇男

    第13回みやぎ眼科塾勉強会　2008/09/26

  80. 線維柱帯切除術が角膜高次収差に与える影響

    布施昇男, 大家義則, 中澤徹, 雪田昌克, 西田幸二

    第19回緑内障学会　2008/09/12

  81. 緑内障

    布施昇男

    第二回県北症例検討会　2008/09/05

  82. Screening for Candidate Genes for Open-angle Glaucoma on Chromosome 2

    布施昇男

    Glaucoma Summer Camp　2008/07/31

  83. 若年者の解放隅角緑内障の診断とフォローについて？遺伝子解析を含めて？

    布施昇男

    福岡県眼科学術講演会　2008/07/19

  84. 緑内障治療の現在と今後 臨床面から

    布施昇男

    第46回北日本眼科学会　2008/07/12

  85. Visual Function with Acupuncture Tested by Visual Evoked Potential International-presentation

    布施昇男

    World Ophthalmic Congress　2008/06/28

  86. 緑内障早期発見に大切な眼底病変の診断について

    布施昇男

    第25回艮の会緑内障眼底読影勉強会　2008/06/13

  87. 産業医が見逃してはならない眼の疾患

    布施昇男

    仙台市医師会勉強会　2008/05/21

  88. 緑内障診断のための眼底読影のポイント

    布施昇男

    郡山眼底読影勉強会　2008/05/17

  89. 分子遺伝学的に緑内障性視神経症（GON）を斬れるか？

    布施昇男

    第6回宮崎緑内障セミナー　2008/05/10

  90. 若年者の解放隅角緑内障の診断とフォローについて

    布施昇男

    第174回宮城県眼科集談会　2008/04/26

  91. 日本人の嚢性緑内障におけるLOXL1遺伝子の解析

    布施昇男, 宮澤晃子, 中澤徹, ムンクガル, 大友孝昭, 清宮基彦, 西田幸二

    第112回日本眼科学会総会　2008/04/17

  92. 緑内障の病態ごとでの治療

    布施昇男

    第9回宮城県薬剤師定例研修会　2008/03/15

  93. 緑内障早期発見に大切な眼底病変の診断について

    布施昇男

    「三陸リアスの会」釜石緑内障眼底読影勉強会　2008/03/14

  94. 若年者の開放隅角緑内障の診断とフォローについて

    布施昇男

    第244回広島眼科症例検討会　2008/03/13

  95. 緑内障診断のための眼底読影のポイント

    布施昇男

    空知地区緑内障眼底読影勉強会　2008/03/01

  96. 一日でcatch up “緑内障分子遺伝学”

    布施昇男

    フロンティア沖縄眼研究会　2008/01/12

  97. 初期緑内障の眼底・視野変化について

    布施昇男

    ファイザー眼科講演会　2007/11/22

  98. 発見できた緑内障の治療とフォローについて

    布施昇男

    第61回日本臨床眼科学会　2007/10/12

  99. マイトマイシンC併用線維柱帯切除術術後の低眼圧黄斑症の発症に関する検討

    布施昇男, 清宮基彦, 大友孝昭, 西田幸二

    第61回日本臨床眼科学会　2007/10/12

  100. 緑内障眼における網膜視神経線維層厚測定値と視野障害との相関の検討

    大友孝昭, 布施昇男, 清宮基彦, 中澤徹, 西田幸二

    第61回日本臨床眼科学会　2007/10/12

  101. ベーチェット病の眼病変治療中に神経ベーチェット病を発症した一例

    清宮基彦, 布施昇男, 大友孝昭, 宮澤弘史, 阿部俊明, 西田幸二

    第61回日本臨床眼科学会　2007/10/12

  102. 眼科救急？外傷を中心として？

    布施昇男

    日医生涯教育講座・救急医療医師研修会　2007/09/20

  103. 緑内障原因遺伝子OPTN遺伝子多型とWDR36遺伝子多型の相互作用の検討

    布施昇男, 宮澤晃子, ムンクガル, 西田幸二

    第18回日本緑内障学会　2007/09/14

  104. NMDAによる網膜視神経節細胞死に対するピタバスタチンの神経保護作用

    中澤徹, 高橋秀肇, 横倉俊二, 布施昇男, 志村雅彦, 西田幸二

    第18回日本緑内障学会　2007/09/14

  105. 緑内障診断のための眼底読影のポイント

    布施昇男

    上越地区眼底読影勉強会　2007/08/04

  106. 緑内障早期発見に大切な眼底病変の診断について

    布施昇男

    福島ひまわり会眼底読影勉強会　2007/06/29

  107. 緑内障視神経乳頭と薬物治療戦略

    布施昇男

    第2回秋田眼科フォーラム　2007/06/16

  108. Screening for Candidate Genes for Open-angle Glaucoma on Chromosome 2 International-presentation

    N.Fuse, Y.Mashima, M.Mengkegale, T.Funayama, A.Miyazawa, K.Nishida

    The Association for Research in Vision and Ophthalmology 2007　2007/05/06

  109. 常染色体2番における開放隅角緑内障原因遺伝子のスクリーニング

    布施昇男, 真島行彦, ムンクガル, 船山智代, 宮澤晃子, 西田幸二

    第111回日本眼科学会総会　2007/04/19

  110. 遺伝子変異による緑内障視神経症

    布施昇男

    第111回日本眼科学会総会　2007/04/19

  111. Axenfeld-Rieger症候群の3例

    布施昇男

    第85回南東北眼科研究会プログラム　2007/03/31

  112. 緑内障早期発見に大切な眼底病変の診断について

    布施昇男

    第2回浜通り眼科勉強会　2007/03/03

  113. 緑内障の治療を考える〜緑内障の早期発見と早期治療

    布施昇男

    第7回青森緑内障談話会　2007/02/18

  114. マイトマイシンC併用線維柱帯切除術術後の低眼圧黄斑症の検討

    布施昇男, 清宮基彦, 大友孝昭, 西田幸二

    第18回みちのく緑内障懇話会　2006/10/29

  115. コントラスト感度視力検査による緑内障に対する鍼治療の視機能評価

    相良淑子, 布施昇男, 中澤徹, 清宮基彦, 関隆志, 西田幸二

    第60回日本臨床学会　2006/10/05

  116. 緑内障3分診療を科学する-youngsterの乳頭を見る-

    布施昇男

    第17回日本緑内障学会　2006/09/08

  117. Enterococcus faecalisによる予後不良な白内障術後眼内炎の1例

    今留尚人, 今井詠子, 布施昇男, 西田幸二

    第44回北日本眼科学会　2006/07/14

  118. Investigation of the Association between WDR36 Polymorphisms and Primary Open Angle Glaucoma and Normal Tension Glaucoma International-presentation

    Fuse N, Miyazawa A, Mengkegale M, Nishida K

    The Association for Research in Vision and Ophthalmology 2006　2006/04/30

  119. 原発開放隅角緑内障（広義）原因遺伝子のWDR36遺伝子の評価

    布施昇男, 宮澤晃子, ムンクガル, 西田幸二

    第110回日本眼科学会総会　2006/04/13

  120. 加齢黄斑変性症におけるComplement factor H遺伝子の解析

    布施昇男, 宮澤晃子, ムンクガル, 吉田まどか, 涌澤亮介, 阿部俊明, 玉井信

    第59回日本臨床眼科学会　2005/10/07

  121. 緑内障患者に対する鍼治療の短期経過観察

    相良淑子, 布施昇男, 中澤徹, 渡邉慶, 清宮基彦, 高橋佳奈, 横倉俊二, 工藤英代, 関隆志, 来須正幸, 玉井信

    第59回日本臨床眼科学会　2005/10/07

  122. 開放隅角緑内障（広義）：遺伝的観点から

    布施昇男

    第16回日本緑内障学会　2005/09/16

  123. 緑内障薬物治療、患者の年齢と治療方針-若い患者に対する治療方針 -

    布施昇男

    第43回北日本眼科学会　2005/07/15

  124. Novel mutation in FOXC1 gene for Axenfeld-Rieger syndrome in Japanese patients International-presentation

    Fuse N, Takahashi K, Yokokura S, Tamai M

    The Association for Research in Vision and Ophthalmology 2005　2005/05/01

  125. 萎縮型加齢黄斑変性症におけるHEMICENTIN-1遺伝子の解析

    布施昇男, 宮澤晃子, 吉田まどか, 涌澤亮介, 阿部俊明, 玉井信

    第109回日本眼科学会総会　2005/03/24

  126. 萎縮

    布施昇男, 宮澤晃子, 吉田まどか, 涌澤亮介, 阿部俊明, 玉井信

    第109回日本眼科学会総会　2005/03/24

  127. 先天緑内障におけるCYP1B1遺伝子の評価

    宮澤晃子, 布施昇男, 高橋佳奈, 清宮基彦, 玉井信

    第109回日本眼科学会総会　2005/03/24

  128. 網膜色素変性症におけるGDxVCCを用いた視神経線維層厚の測定結果

    清宮基彦, 佐藤肇, 布施昇男, 玉井信

    第109回日本眼科学会総会　2005/03/24

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Research Projects 20

  1. 多層臨床データの情報数理解析と幹細胞医学・発生工学の融合による加齢性難聴研究

    藤岡 正人, 佐々木 貴史, 鈴木 淳, 新井 康通, 布施 昇男, 佐野 肇, 務台 英樹, 吉川 欣亮, 小川 元之, 岩月 正人, 水足 邦雄

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(A)

    Institution: 北里大学

    2024/04/01 - 2027/03/31

  2. ゲノム反復多型伸長変動と認知機能低下を伴う前臨床期神経変性筋疾患の遺伝病態の解明

    平良摩紀子, 岡村容伸, 布施昇男, 三木篤也, 田高周

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2024/04 - 2027/03

  3. Risk profiling for cardiovascular diseases using the retinal images

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Osaka University

    2022/04/01 - 2026/03/31

  4. Risk profiling for cardiovascular diseases using the retinal images

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Osaka University

    2022/04/01 - 2026/03/31

  5. モバイルヘルスとゲノミクスの融合によるドライアイの多様性理解と層別化医療の実現

    猪俣 武範, 布施 昇男, 清水 厚志, 中村 正裕

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 順天堂大学

    2023/06/30 - 2025/03/31

  6. 光が乳癌発症に与える影響に関する基盤研究

    濱中 洋平, 石田 孝宣, 布施 昇男

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04/01 - 2024/03/31

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    これまで多くの疫学研究によって乳癌罹患に関わるリスク因子が解明されたが、いまだ日本人女性の乳癌罹患数を減らすには至っていない。メラトニンは脳の松果体で分泌される内分泌物質で、エス トロゲンを抑制することが知られており、網膜への光刺激で分泌が抑制される。以前より、電磁波や夜間の電光暴露によるメラトニン減少が乳癌の発症率を増加させているという“メラトニン仮説”が報告されている。 本研究は、東北メディカル・メガバンク計画によるゲノムコホート調査から、光とメラトニン、乳癌発症に関するデータを可能なかぎり抽出して、将来的に日本人女性の光環境を変化させることで乳癌罹患数を低減できる可能性をもとに、その基盤となるデータを集積することを目的とする。 ゲノムコホート調査から抽出可能なデータとして、１．OCT(Optical Coherence Tomography)による網膜所見および網膜厚、２．脳MRIによる松果体体積、３．全ゲノム解析によるメラトニン合成酵素のバリアント、４．唾液中のメラトニン定量値、５．睡眠および日中の活動性、眠剤内服の情報、があげられる。本研究では、これらのデータのうち現時点で抽出可能なものを抽出し、乳癌既往の有無の情報と突合する手法をとる。 現在のところコホート調査およびそのデータ解析は計画にそって順調に進められ、データの蓄積が進んでいる。本年度は、データ構成の把握と抽出方法および解析手法についての検討を行ない、来年度以降のデータ解析の基盤を構築した。

  7. Cerebral white matter lesions and cerebral small vessel disease-related gene variants in the Japanese general population

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Kyoto Prefectural University of Medicine

    2021/04/01 - 2024/03/31

  8. 網膜層厚と遺伝環境因子による孤発性晩期発症型アルツハイマー病前臨床期診断法の確立

    平良 摩紀子, 布施 昇男, 川崎 良, 三木 篤也, 小島 要, 田高 周

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04/01 - 2024/03/31

  9. 乳癌罹患リスク低減に向けた遺伝子多型、生活習慣、血漿メタボロームの統合解析

    石田 孝宣, 寳澤 篤, 布施 昇男, 濱中 洋平, 小柴 生造, 栗山 進一

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2020/04/01 - 2023/03/31

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    乳癌死亡数を減らすためには、個々の女性の乳癌罹患リスクを的確に評価し、そのリスクを低減することは重要な課題である。本研究は、日本人女性が自分の遺伝子多型と血漿メタボローム情報をもとに、乳癌罹患リスクを低減するために生活習慣をどのように改善すればよいかを知り、その効果を血漿メタボローム変化で知る個別化予防の構築を目的とする。 本研究はToMMoおよび大学病院のバイオバンクを利活用して、一般住民と乳癌患者の遺伝子多型、生活習慣、血漿メタボロームのデータを用いて解析する。乳癌罹患リスクに関連のある84の遺伝子多型、8つの血漿代謝物、改善・変更可能な身体情報・生活習慣（食習慣、住環境、睡眠、運動、嗜好、内服薬など）、および乳癌罹患の情報を用いて解析を行う。 コホート参加者の生活調査は登録時に行われており、全コホート参加者の全ゲノムシークエンスもしくはアレイ解析によるゲノム解析、血漿メタボローム解析が進められている。メタボローム解析は、NMR、GC-MS、LC-MSの3法が用いられおり、標的メタボローム解析法のMXp Quant 500 Kitを用いたLC-MS解析（500代謝物）は1,000人以上の成人女性に行われる予定である。 東北大学病院に通院している乳癌既往者約1,700人のうち、乳癌術後の無再発患者は約1,300人である。2021年度末には、計約800人が登録して血液検体保存がされる見込みであり、2022年度以降に、ToMMoが開発したSNPアレイであるジャポニカアレイNEOを用いたゲノム解析およびMXp Quant 500 Kitを用いたLC-MS解析を行う計画である。 以上の全体の研究実施計画のうち、2021年度は、大学病院においては乳癌患者のバイオバンク登録をすすめるとともに、メタボローム解析を行うためのデータ整理を行った。

  10. Development of new OCT parameters for early detection of glaucoma

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Osaka University

    2019/04/01 - 2023/03/31

  11. 次世代シークエンサーを用いた新規緑内障原因遺伝子の検索 Competitive

    布施 昇男

    Offer Organization: 日本学術振興会

    System: 基盤研究（Ｃ）

    2019 - 2021

  12. Genome-wide DNA analysis on people with family name "Japan" in Spain who are presumed as descendants of a part of the delegation to Rope by Masamune Date

    Yamamoto Toshimichi, TOKUNAGA Katsushi, FUSE Nobuo, KAWAI Yosuke, CARRACEDO Angel

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Nagoya University

    2012/04/01 - 2017/03/31

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    Among 800 people with family name indicated “Japan” in Spanish lived in Coria del Rio near Seville in Spain, 50 males and 51 females wishfully donated their blood with written informed consents to perform DNA analyses to confirm tips of Japanese traces on their genomes scientifically. DNA samples were extracted in by collaborators Spain, and all of the DNA analyses were performed in Japan. Unfortunately, the results of Y-STR (STRs on Y chromosome) haplotype analysis for male samples, all of the haplotypes were not similar to Japanese ones, but close to Spanish or other countries' ones. Genome-wide SNP analysis with the Japonica Array where almost all of about 660K SNPs were specific to Japanese genome also could not revealed any Japanese traces on their genomes by comparing with those data from 8 indigenous Japanese and in Tohoku Medical Mega Bank, and from Spain DNA Bank. In future, other newly improved and developed techniques or analyses would be successful to certify this matter.

  13. 次世代シークエンサーを駆使した希少遺伝性難病の原因解明と治療法開発の研究 Competitive

    布施 昇男

    Offer Organization: 厚生労働省

    System: 科学研究費補助金（難病・がん等の疾患分野の医療の実用化研究事業）

    2011 - 2014

  14. Identification for glaucoma related genes and application for diagnosis and pharmacogenomics Competitive

    FUSE Nobuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2010 - 2012

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    We have done the screening for the glaucoma genes using the single nucleotide polymorphisms (SNPs). Using association study, we identified the glaucoma susceptibility genes for primary open angle glaucoma, normal tension glaucoma, and exfoliation glaucoma. We also detect the rare amino acid substitutions in glutamate transporter gene GLAST by candidate gene approach. By the association study using SNPs and candidate gene approach, we detected glaucoma susceptibility genes.

  15. Screening for Glaucoma causal gene for tailor-made medicine in Japanese population Competitive

    FUSE Nobuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2006 - 2007

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    We have done the screening for glaucoma-causal gene MYOC and WDR 36 in Japanese population, and did association analysis between phenotype and genotype comparing with normal subjects. Subjects were Primary Open Angle Glaucoma (POAG), Normal Tension Glaucoma (NTG) and Normal Subjects. In MYOC gene, we found the early onset two POAG pedigrees related with Ala363Thr mutation, and one POAG subject related with Asn297His mutation (MengGe M, ed. Al. Mol Vis.2007). In WDR36 gene, we found Ser664Leu in POAG subject, and revealed that Ile264Val, IVS16-30A/G were associated with phenotype of visual field defect of POAG (Miyazawa A, ed. Al. Mol Vis.2007). Beside the POAG/NTG; we found Ala85Pro mutation and 437-453de117 in FOXC1 gene in Axenfeld-Rieger syndrome, which is one form of congenital glaucoma (Fuse N, ed. Al. Mol Vis.2007) As a result, we identified the new information as follows: 1) the distribution of MYOC mutations is same as that of Caucasians, but the positions are different 2) the distribution of WDR36 mutations is different from that of Caucasians, and related with phenotype of POAG 3) the spectrum of FOXC1 mutation is unique to Japanese. Those results will be helpful for genetic testing for glaucoma in near future.

  16. 神経栄養因子分泌細胞含有ゴアテックス膜による視細胞保護

    阿部 俊明, 布施 昇男, 鵜殿 徹男

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽研究

    Institution: 東北大学

    2005 - 2005

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    我々は神経栄養因子を分泌する培養色素上皮細胞の網膜下移植は連続光照射などの視細胞傷害に対して視細胞保護効果があることを報告してきた。栄養因子分泌にはウイルスベクターを使用するのではなく、すでに日本で臨床応用されているリポゾームを使用し、遺伝子が導入された細胞のみを選択培養した。このことで一過性の神経栄養分泌ではなく永続的な分泌が得られ、長時間の培養後でも移植後に保護効果があることを報告した.網膜色素変性などの臨床経過から考えても、これらの操作を行う時間的な余裕はあり、将来の臨床応用を考えても倫理的な問題の多くをクリアできると考えられた。一方、ゴアテックス膜やコラーゲン膜は生体適合性が優れ、広く生体内に使用されている。この膜を強膜半層(かなり全層に近く)切開後に強膜下に移植できる。強膜下移植のために視細胞周囲の微細環境は移植手技などで、破壊されないですむ。今回はこの両膜に栄養因子分泌細胞を培養することを試みた。まず、コラーゲン膜は我々が開発した方法で強化すると6ヶ月以上培養しても、培地中にコラーゲン膜が溶け出すことはなく、膜はセッシで容易に把持できた。また、継時的に培養細胞の生存を確認でき目的の神経栄養因子が分泌されていることもELISAとwestern blottingで確認できた。組織学的な観察では培養細胞と異なり、細胞は膜内で立体的な構造を保っていることが判明した.ゴアテックス膜はさらに強度が高い分、細胞の膜内侵入は当初は困難であったが、さまざまな工夫を利用し、培養細胞を変更することで膜内培養が可能であった.

  17. Evaluation of protective and adverse effects of gene transferred IPE cell transplantation on degenerative retinal diseases

    TAMAI Makoto, NAKAGAWA Yoichi, FUSE Nobuo, SATO Hajime, TOMITA Hiroshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2003 - 2004

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    We have been trying a clinical approach to the patients with AMD by transplantation of autologous cultured IPE cells. More than 80% of the patients showed an improvement of visual acuity after the transplantation. However the best visual acuity in these patients was still far from sufficient effect. These reports suggested that there is a limitation in the use of autologous IPE cells for transplantation. We investigated the stable and safety gene transduction to IPE cells. The purpose of this study is to demonstrate the effect of the neurotrophic factors-transduced cells and safety of vector to use gene transfer. The stability of transgene expression in the retina was needed for gene therapy. One of methods to transduce a gene into relevant cells is to use virus vectors. Now we can use various type of virus vectors. The recombinant adeno-associated virus (rAAV) has proven to be an efficient and effective vector. We studied the transduction efficiency to IPE cells by using 5 types of AAV serotypes. These results revealed that serotype 2 (rAAV2) is the most effective vector for gene therapy in IPE cells. But the trasduction efficiency was less than 20%. To improve this problem, we studied the manner of virus infection and revealed that the pre-treatment with tyrphostin-1 (epidermal growth factor receptor tyrosine kinase inhibitor) led to increase of AAV2-transduction. The neuroprotective effect of AAV BDNF transduced IPE cells (BDNF-IPE) on the retinal ganglion cells (RGCs) were assessed. In vitro, BDNF deprivation RGC death was significantly suppressed by HUSB-Tyr treated-BDNF-IPE. In vivo model of photoreceptor degeneration caused by continuous light exposure, transplantation of HUSB-Tyr-treated-BDNF-IPE inhibited photoreceptor degeneration.

  18. 網膜及び網膜色素上皮細胞の分化を制御する、新規の転写因子の単離とその機能解析

    布施 昇男

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 東北大学

    1999 - 2000

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    加齢黄斑変性は近年ますます増加している、高度の視力障害をきたす疾患である。その背景には環境的な危険因子とともに遺伝的な要素も関係していると考えられる。最近加齢黄斑変性において、Starg ardt病の原因遺伝子であるABCR(Retina-specific ATP binding cassette trans porter)に13の遺伝子異常があることが報告された。ABCR mRNAは網膜に特異的に発現している。今回、日本人の萎縮型加齢黄斑変性とABCR遺伝子の異常に関連性があるか検討した。東北大学眼科外来で、萎縮型加齢黄斑変性と診断された25例の患者からinformed consentに基づいて末梢血を採取し、加齢黄斑変性を認めない40例の患者を対照群とした。genomeDNAを抽出し、目的の26個のexonをPCR法で増幅した。得られたPCR産物をすべてdirect sequence法にて塩基配列を決定し解決した。 ABCR遺伝子のexon23に全例でP1116S,H1125L,Q1126Lの塩基置換が存在したが、これは対照群においても全例に存在した。exon29に報告された変異と同じT1428Mのアミノ酸変異が1例認められた(1/25;4%)が、この変異は対照群にも認められた(2/40;5%)。Starg ardt病における既知のポリモルフィズムと同じI2083Iが2例認められた。intron33にヘテロの塩基置換が4例、ホモの塩基置換が2例認められた。Allikmetsらは加齢黄斑変性の16%にABCR遺伝子の異常があると報告したが、今回の検討ではこれを支持する結果は得られなかった。ABCRが網膜疾患にどう関わっているか明らかにするためには、ABCRの機能及び遺伝子の発現調節機構の解明も必要であると思われ、今後の課題と考えられる。

  19. Auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration : basic and clinical research

    TAMAI Makoto, ABE Toshiaki, NAKAGAWA Youichi, SATO Hajime, WADA Yuko, TOMITA Hiroshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    1998 - 2000

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    Purpose. To establish autologous iris pigment epitheial cell transplantation in patients with age related macular degeneration. We investgated the survival of transplanted. IPE cells in monkey eye. Methods. Autologous IPE cells from three monkeys were obtained by peripheral iridectomy, and cells were performed with autologous serum. The cultured cells were labeled with DiI, and transplantation was performed by transvitreal approach to submacular region of each monkey. Fundus examination, photography, and fluorescein angiography were performed monthly. Histochemical analysis and electron microscopy were also performed six monthsafter transplantation Results. Auto IPE cells grew well in auto serum. No fluorescein leakage or retinal thickening was observed after submacular transplantation. We demonstrated the presence of autologous IPE cells in the resion 6months after transplantation by histlogic and electron microscopy also demonstrated that the transplanted cells appeared to be less pigmented and to have less mitchondoria than did the host retinal pigment epithelial cells. However, some transplanted cells looked as if they embrace the photoreceptor outer segments. Discussion. Autologous IPE cell culture of the monkey was established using auto serum. Six months after transplantaiton of of cultured IPE cells, we could still observe the cells in region. This method may have potential use in human desiese that reqires autologous cell transplantation to prevent host-graft rejection, and to provide an alternative substance that functions like retinal pigment epithelium

  20. 緑内障早期発見を目指した多遺伝子リスクスコア評価法の構築

    System: 学術振興会科学研究費基盤研究（C） 2022－2024年

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  1. 自家培養口腔粘膜上皮シート移植による角膜上皮再生治療法の多施設共同臨床試験

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    培養口腔粘膜上皮細胞シート移植法の多施設共同臨床研究を実施し、その有効性と安全性を検討する

  2. テーラーメード医療のための緑内障遺伝子・感受性遺伝子の解析

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    テーラーメード医療のための緑内障遺伝子・感受性遺伝子の解析

  3. 正常眼圧緑内障の病態解明と治療薬の開発

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    正常眼圧緑内障の病態解明と治療薬の開発

  4. オーダーメード医療を目指した緑内障原因遺伝子・感受性遺伝子の解析

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    オーダーメード医療を目指した緑内障原因遺伝子・感受性遺伝子の解析