Details of the Researcher

PHOTO

Atsushi Shimizu
Section
Tohoku Medical Megabank Organization
Job title
Professor
Degree

  • Doctor of Science (Aoyam)

e-Rad No.
30327655

Research History 16

  • 2026/04 - Present
    National Institute of Genetics

  • 2026/04 - Present
    Tohoku University　Tohoku Medical Megabank Organization　Professor

  • 2025/09 - Present
    Keio University　School of Medicine Department of Preventive Medicine and Public Health　Professor

  • 2022/04 - 2026/03
    National Institute of Genetics　Bioinformation and DDBJ Center　Professor

  • 2020/05 - 2026/03
    Tohoku University　Tohoku Medical Megabank Organization

  • 2020/01 - 2025/12
    岩手医科大学　Division of Biomedical Information Analysis, Institute for Biomedical Sciences　Professor

  • 2019/08 - 2025/03
    Keio University　School of Medicine, Department of Preventive Medicine and Public Health　Professor

  • 2013/04 - 2024/03
    Keio University　School of Medicine, Department of Physiology

  • 2018/09 - 2022/03
    National Institute of Genetics　DDBJ Center　Project Professor

  • 2013/03 - 2019/12
    Iwate Medical University　Iwate Tohoku Medical Megabank Organization　Professor

  • 2013/02 - 2013/02
    Keio University　School of Medicine, Department of Molecular Biology　Associate Professor

  • 2012/10 - 2013/01
    Keio University　School of Medicine, Department of Molecular Biology　Assistant Professor

  • 2007/04 - 2012/09
    Keio University　School of Medicine, Department of Molecular Biology　Instructor

  • 2004/05 - 2007/03
    Keio University　School of Medicine, Department of Molecular Biology　Instructor

  • 2000/04 - 2004/04
    Keio University　School of Medicine, Department of Molecular Biology　Instructor (Non-tenured)

  • 1999/07 - 2000/03
    Keio University　School of Medicine, Department of Molecular Biology　Researcher (Non-tenured)

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Education 2

  • Aoyama Gakuin University　Graduate School of Science and Engineering

    1994/04 - 1999/03

  • Aoyama Gakuin University　College of Science and Engineering　Department of Chemistry

    1900/04 - 1994/03

Committee Memberships 4

  • 日本疫学会疫学　リソース利用促進委員会リンケージ基盤推進ワーキンググループ委員

    2022/01 - Present

  • 日本人類遺伝学会　利益相反委員会委員

    2019/11 - Present

  • 日本人類遺伝学会　評議員

    2019/11 - Present

  • 日本バイオインフォマティクス学会　理事

    2018/04 - 2020/03

Professional Memberships 9

  • American Society of Human Genetics

  • THE JAPAN SOCIETY OF HUMAN GENETICS

  • THE JAPANESE SOCIETY FOR GENETIC COUNSELING

  • NGS現場の会

  • 日本オミックス医療学会

  • 日本エピジェネティクス研究会

  • THE KEIO MEDICAL SOCIETY

  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

  • 日本遺伝子診療学会

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Research Interests 6

  • バイオインフォマティクス

  • 次世代シークエンサー

  • 疫学

  • 遺伝医学

  • ゲノム医学

  • Molecular genetics

Research Areas 4

  • Life sciences / Fetal medicine/Pediatrics /

  • Life sciences / Medical biochemistry /

  • Life sciences / Systems genomics /

  • Life sciences / Genomics /

Awards 1

  1. 第23回日本抗加齢医学会総会最優秀演題賞

    2023/06　日本抗加齢医学会　日本人に最適化した新規エピゲノムクロックの開発

Papers 188

  1. Reference-Based Standardization Approach Stabilizing Small Batch Risk Prediction via Polygenic Score. International-journal Peer-reviewed

    Yoichi Sutoh, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Tomoharu Tokutomi, Akiko Yoshida, Yuka Kotozaki, Shohei Komaki, Shiori Minabe, Hideki Ohmomo, Kozo Tanno, Akimune Fukushima, Makoto Sasaki, Atsushi Shimizu

    Genetic epidemiology　49　(2)　e70002　2025/03

    DOI： 10.1002/gepi.70002 　

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    The polygenic score (PGS) holds promise for motivating preventive behavioral changes. However, no clinically validated standardization methodology currently exists. Here, we demonstrate the efficacy of a "reference-based" approach for standardization. This method uses the PGS distribution in the general population as a reference for normalization and percentile determination; however, it has not been validated. We investigated three potential influences on PGS computation: (1) the size of the reference population, (2) biases associated with different genotyping platforms, and (3) inclusion of kinship ties within the reference group. Our results indicate that the reference size affects the bootstrap estimate of standard error for PGS percentiles, peaking around the 50th percentile and diminishing at extreme percentiles (1st or 100th). Discrepancies between genotyping platforms, such as different microarrays and whole-genome sequencing, resulted in deviations in PGS (p < 0.05 in Kolmogorov-Smirnov test). However, these deviations were reduced to a nonsignificant level using shared genetic variants in the calculations when the ancestry of the samples and reference were matched. This approach recovered approximately 9.6% of the positive predictive value of PGS by naïve genotype. Our results provide fundamental insights for establishing clinical guidelines for implementing PGS to communicate reliable risks to individuals.

  2. Influence of physical activity on the epigenetic clock: evidence from a Japanese cross-sectional study. International-journal Peer-reviewed

    Masatoshi Nagata, Shohei Komaki, Yuichiro Nishida, Hideki Ohmomo, Megumi Hara, Keitaro Tanaka, Atsushi Shimizu

    Clinical epigenetics　16　(1)　142-142　2024/10/15

    DOI： 10.1186/s13148-024-01756-1 　

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    BACKGROUND: Biological age, especially epigenetic age derived from the epigenetic clock, is a significant measure of aging, considering the differences in aging rates among individuals. The epigenetic clock, a machine learning-based algorithm, uses DNA methylation states to estimate biological age. Previous studies have reported inconsistent associations between physical activity (PA) and the epigenetic clock, especially second-generation clocks such as PhenoAge and GrimAge. This study aimed to clarify this relationship using cross-sectional data from Japanese participants aged 40-69. METHODS: We used two datasets from the Saga J-MICC study, of which 867 samples were available for analysis. DNA methylation data from peripheral blood samples were used to calculate the epigenetic age using the epigenetic clocks PhenoAge and GrimAge. PA and sedentary time were measured using a single-axis accelerometer, while self-reported PA, sedentary time, and covariates were assessed using a self-administered questionnaire. The association between PA or sedentary time and epigenetic age acceleration was assessed using multiple linear regression. RESULTS: Pearson's correlation coefficients between accelerometer-based and self-reported PA variables ranged from 0.09 to 0.20. Multivariable regression analysis showed that accelerometer-based PA and sedentary time were associated with epigenetic age decelerations and accelerations, respectively. However, self-reported PA was not associated with the epigenetic age accelerations. CONCLUSIONS: These results indicate that reducing sedentary time and increasing PA were associated with slowing both PhenoAge and GrimAge, even in East Asian populations with different exercise habits, body shapes, and lifestyles. This study highlights the potential of objective second-generation epigenetic age acceleration as an outcome index for healthcare interventions and clinical applications.

  3. Healthy lifestyle practice correlates with decreased obesity prevalence in individuals with high polygenic risk: TMM CommCohort study. International-journal Peer-reviewed

    Yoichi Sutoh, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Shohei Komaki, Shiori Minabe, Hideki Ohmomo, Makoto Sasaki, Atsushi Shimizu

    Journal of human genetics　2024/08/22

    DOI： 10.1038/s10038-024-01280-3 　

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    Obesity and overweight, fundamental components of the metabolic syndrome, predispose individuals to lifestyle-related diseases. The extent to which adopting healthy lifestyles can reduce obesity risk, even in those with a high genetic risk, remains uncertain. Our aim was to assess the extent to which lifestyle modifications can improve outcomes in individuals with a high polygenic score (PGS) for obesity. We quantified the genetic risk of obesity using PGSs. Four datasets from the Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) were employed in the study. One dataset (n = 9958) was used to select the best model for calculating PGS. The remaining datasets (total n = 69,341) were used in a meta-analysis to validate the model and to evaluate associated risks. The odds ratio (OR) for obesity risk in the intermediate (11th-90th percentiles in the dataset) and high PGS categories (91st-100th) was 2.27 [95% confidence intervals: 2.12-2.44] and 4.83 [4.45-5.25], respectively, compared to that in the low PGS category (1st-10th). Trend analysis showed that an increase in leisure-time physical activity was significantly associated with reduced obesity risk across all genetic risk categories, representing an OR of 0.9 [0.87-0.94] even among individuals in the high PGS category. Similarly, sodium intake displayed a positive association with obesity across all genetic risk categories, yielding an OR of 1.24 [1.17-1.31] in the high PGS category. The risk of obesity was linked to the adoption of healthy lifestyles, even in individuals with high PGS. Our results may provide perspectives for integrating PGSs into preventive medicine.

  4. Epigenetic profile of Japanese supercentenarians: a cross-sectional study Peer-reviewed

    Shohei Komaki, Masatoshi Nagata, Eri Arai, Ryo Otomo, Kanako Ono, Yukiko Abe, Hideki Ohmomo, So Umekage, Natsuko O Shinozaki, Tsuyoshi Hachiya, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Yasumichi Arai, Nobuyoshi Hirose, Akio Yoneyama, Hideyuki Okano, Makoto Sasaki, Yae Kanai, Atsushi Shimizu

    The Lancet Healthy Longevity　4　(2)　e83-e90　2023/02

    Publisher: Elsevier BV

    DOI： 10.1016/s2666-7568(23)00002-8 　

    ISSN： 2666-7568

  5. Evaluation of short-term epigenetic age fluctuation International-journal Peer-reviewed

    Shohei Komaki, Hideki Ohmomo, Tsuyoshi Hachiya, Yoichi Sutoh, Kanako Ono, Ryohei Furukawa, So Umekage, Yayoi Otsuka-Yamasaki, Shiori Minabe, Akira Takashima, Kozo Tanno, Makoto Sasaki, Atsushi Shimizu

    Clinical Epigenetics　14　(1)　76-76　2022/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1186/s13148-022-01293-9 　

    ISSN： 1868-7075

    eISSN： 1868-7083

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    Abstract Considerable effort has been spent on lowering and maintaining the epigenetic age. However, the extent to which epigenetic age fluctuates under normal conditions is poorly understood. Therefore, we analyzed methylation data from monocytes and peripheral blood mononuclear cells collected from two Japanese men. The ranges of the Pan-tissue, Skin and blood, and DNAm PhenoAge epigenetic age during 3 months were ≥ 5.62, ≥ 3.04, and ≥ 8.23 years, and the maximum daily changes were 5.21, 3.20, and 6.53 years, respectively. These fluctuations were not suppressed by correcting for cell-type composition. Although the underlying biological mechanism remains unclear, there was a nonnegligible degree of age fluctuation which should inform personalized clinical applications.

  6. Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study Peer-reviewed

    Hideki Ohmomo, Shohei Komaki, Yoichi Sutoh, Tsuyoshi Hachiya, Kanako Ono, Eri Arai, Hiroyuki Fujimoto, Teruhiko Yoshida, Yae Kanai, Koichi Asahi, Makoto Sasaki, Atsushi Shimizu

    Epigenetics Communications　2　(1)　2022/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1186/s43682-022-00009-7 　

    eISSN： 2730-7034

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    Abstract Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for the early detection and treatment of ccRCC. Results To identify ccRCC-associated DNAm markers, we performed targeted bisulfite sequencing (TB-seq) and an epigenome-wide association study (EWAS) using whole blood-derived DNA from 50 ccRCC patients and 50 healthy controls in the discovery phase. EWAS was performed using a linear regression model. The analysis was adjusted for age, sex, and the estimated cell-type composition. In the replication phase, the accuracy of the identified ccRCC-associated CpGs was verified in 48 independent ccRCC patients and 48 healthy controls. We identified six ccRCC-associated hypomethylated CpGs in PCBD2/MTND4P12 in the discovery phase (p &lt; 1.75 × 10−8); four were reproducible in the replication phase (p &lt; 2.96 × 10−8). The sum of the DNAm levels at the six CpGs was a valid indicator of ccRCC both in the discovery phase (area under the receiver operating characteristic curve [AUC-ROC] = 0.922) and in the replication phase (AUC-ROC = 0.871). Moreover, the results of cis-expression quantitative methylation analysis suggested that the DNAm levels of the ccRCC-associated CpGs affect the gene expression of transcription factor 7 (TCF7) and voltage-dependent anion-selective channel 1 (VDAC1), which are involved in cancer progression. Conclusions In this study, we identified six ccRCC-associated CpGs in PCBD2/MTND4P12 by EWAS using blood-based DNA. We found that the DNAm levels of the six CpGs in PCBD2/MTND4P12 may be a potential biomarker for early ccRCC detection, but the value as a biomarker needs to be investigated in future studies.

  7. The Human Genome Project and the Complete Human Genome Sequencing Invited Peer-reviewed

    Atsushi SHIMIZU

    JSBi Bioinformatics Review　3　(1)　11-19　2022/06/02

    DOI： 10.11234/jsbibr.2022.primer2 　

  8. DNA Methylation Abnormalities and Altered Whole Transcriptome Profiles after Switching from Combustible Tobacco Smoking to Heated Tobacco Products. International-journal Peer-reviewed

    Hideki Ohmomo, Sei Harada, Shohei Komaki, Kanako Ono, Yoichi Sutoh, Ryo Otomo, So Umekage, Tsuyoshi Hachiya, Kota Katanoda, Toru Takebayashi, Atsushi Shimizu

    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology　31　(1)　269-279　2022/01

    DOI： 10.1158/1055-9965.EPI-21-0444 　

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    BACKGROUND: The use of heated tobacco products (HTP) has increased exponentially in Japan since 2016; however, their effects on health remain a major concern. METHODS: Tsuruoka Metabolome Cohort Study participants (n = 11,002) were grouped on the basis of their smoking habits as never smokers (NS), past smokers (PS), combustible tobacco smokers (CS), and HTP users for <2 years. Peripheral blood mononuclear cells were collected from 52 participants per group matched to HTP users using propensity scores, and DNA and RNA were purified from the samples. DNA methylation (DNAm) analysis of the 17 smoking-associated DNAm biomarker genes (such as AHRR, F2RL3, LRRN3, and GPR15), as well as whole transcriptome analysis, was performed. RESULTS: Ten of the 17 genes were significantly hypomethylated in CS and HTP users compared with NS, among which AHRR, F2RL3, and RARA showed intermediate characteristics between CS and NS; nonetheless, AHRR expression was significantly higher in CS than in the other three groups. Conversely, LRRN3 and GPR15 were more hypomethylated in HTP users than in NS, and GPR15 expression was markedly upregulated in all the groups when compared with that in NS. CONCLUSIONS: HTP users (switched from CS <2 years) display abnormal DNAm and transcriptome profiles, albeit to a lesser extent than the CS. However, because the molecular genetic effects of long-term HTP use are still unknown, long-term molecular epidemiologic studies are needed. IMPACT: This study provides new insights into the molecular genetic effects on DNAm and transcriptome profiles in HTP users who switched from CS.

  9. Longitudinal DNA methylation dynamics as a practical indicator in clinical epigenetics. International-journal Peer-reviewed

    Shohei Komaki, Hideki Ohmomo, Tsuyoshi Hachiya, Yoichi Sutoh, Kanako Ono, Ryohei Furukawa, So Umekage, Yayoi Otsuka-Yamasaki, Kozo Tanno, Makoto Sasaki, Atsushi Shimizu

    Clinical epigenetics　13　(1)　219-219　2021/12/13

    DOI： 10.1186/s13148-021-01202-6 　

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    BACKGROUND: One of the fundamental assumptions of DNA methylation in clinical epigenetics is that DNA methylation status can change over time with or without interplay with environmental and clinical conditions. However, little is known about how DNA methylation status changes over time under ordinary environmental and clinical conditions. In this study, we revisited the high frequency longitudinal DNA methylation data of two Japanese males (24 time-points within three months) and characterized the longitudinal dynamics. RESULTS: The results showed that the majority of CpGs on Illumina HumanMethylation450 BeadChip probe set were longitudinally stable over the time period of three months. Focusing on dynamic and stable CpGs extracted from datasets, dynamic CpGs were more likely to be reported as epigenome-wide association study (EWAS) markers of various traits, especially those of immune- and inflammatory-related traits; meanwhile, the stable CpGs were enriched in metabolism-related genes and were less likely to be EWAS markers, indicating that the stable CpGs are stable both in the short-term within individuals and under various environmental and clinical conditions. CONCLUSIONS: This study indicates that CpGs with different stabilities are involved in different functions and traits, and thus, they are potential indicators that can be applied for clinical epigenetic studies to outline underlying mechanisms.

  10. Genome-Wide Polygenic Score and the Risk of Ischemic Stroke in a Prospective Cohort: The Hisayama Study. International-journal Peer-reviewed

    Tsuyoshi Hachiya, Jun Hata, Yoichiro Hirakawa, Daigo Yoshida, Yoshihiko Furuta, Takanari Kitazono, Atsushi Shimizu, Toshiharu Ninomiya

    Stroke　51　(3)　759-765　2020/03

    DOI： 10.1161/STROKEAHA.119.027520 　

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    Background and Purpose- Environmental and genetic factors contribute to the development of ischemic stroke (IS). We recently developed a genome-wide polygenic risk score (PRS) for IS using case-control datasets from 4 large-scale observational studies conducted in Japan. Our objective in the present study was to confirm the association between the PRS and the risk of IS with data from an independent prospective cohort recruited from the general Japanese population. Methods- A total of 3038 subjects aged ≥40 years were followed up for 10 years (2002-2012). The genome-wide PRS was calculated using genotype data from >350 000 single-nucleotide polymorphisms. The PRS levels were divided into quintiles. High and low genetic risk groups were defined as top 60% and bottom 40% of PRS, respectively. The hazard ratio (HR) for the development of IS was estimated using a Cox proportional hazards model. Results- During the follow-up period, 91 cases developed first-ever IS. The age- and sex-adjusted HR for IS increased with higher PRS levels (P for trend, 0.03). Subjects with the highest quintile level of PRS had a 2.44-fold (95% CI, 1.16-5.12) greater risk for IS than those with the lowest quintile level after adjusting for age and sex. A similar association was observed after adjusting for environmental risk factors (P for trend, 0.03). As compared with low genetic risk group, the age- and sex-adjusted HR in high genetic risk group was 1.63 (95% CI, 1.04-2.55), which was comparable to the HR of hypertension (HR, 1.41), diabetes mellitus (HR, 1.72), and smoking (HR, 1.54). The age- and sex-adjusted HR increased with the number of environmental risk factors in both high and low genetic risk groups without significant interaction. Conclusions- A high genome-wide PRS was a significant risk factor for IS independent of environmental risk factors in a general Japanese population. This finding suggests that PRS may be useful to identify individuals at a high risk of IS.

  11. Population-based biobank participants' preferences for receiving genetic test results Peer-reviewed

    Kayono Yamamoto, Tsuyoshi Hachiya, Akimune Fukushima, Naoki Nakaya, Akira Okayama, Kozo Tanno, Fumie Aizawa, Tomoharu Tokutomi, Atsushi Hozawa, Atsushi Shimizu

    JOURNAL OF HUMAN GENETICS　62　(12)　1037-1048　2017/12

    DOI： 10.1038/jhg.2017.81 　

    ISSN： 1434-5161

    eISSN： 1435-232X

  12. 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

  13. Genetic Predisposition to Ischemic Stroke: A Polygenic Risk Score Peer-reviewed

    Tsuyoshi Hachiya, Yoichiro Kamatani, Atsushi Takahashi, Jun Hata, Ryohei Furukawa, Yuh Shiwa, Taiki Yamaji, Megumi Hara, Kozo Tanno, Hideki Ohmomo, Kanako Ono, Naoyuki Takashima, Koichi Matsuda, Kenji Wakai, Norie Sawada, Motoki Iwasaki, Kazumasa Yamagishi, Tetsuro Ago, Toshiharu Ninomiya, Akimune Fukushima, Atsushi Hozawa, Naoko Minegishi, Mamoru Satoh, Ryujin Endo, Makoto Sasaki, Kiyomi Sakata, Seiichiro Kobayashi, Kuniaki Ogasawara, Motoyuki Nakamura, Jiro Hitomi, Yoshikuni Kita, Keitaro Tanaka, Hiroyasu Iso, Takanari Kitazono, Michiaki Kubo, Hideo Tanaka, Shoichiro Tsugane, Yutaka Kiyohara, Masayuki Yamamoto, Kenji Sobue, Atsushi Shimizu

    STROKE　48　(2)　253-258　2017/02

    DOI： 10.1161/STROKEAHA.116.014506 　

    ISSN： 0039-2499

    eISSN： 1524-4628

  14. Intraindividual dynamics of transcriptome and genome-wide stability of DNA methylation Peer-reviewed

    Ryohei Furukawa, Tsuyoshi Hachiya, Hideki Ohmomo, Yuh Shiwa, Kanako Ono, Sadafumi Suzuki, Mamoru Satoh, Jiro Hitomi, Kenji Sobue, Atsushi Shimizu

    SCIENTIFIC REPORTS　6　26424　2016/05

    DOI： 10.1038/srep26424 　

    ISSN： 2045-2322

  15. Genome-wide association study of social isolation in 63,497 Japanese individuals from the general population. International-journal

    Hisashi Ohseto, Kosuke Inoue, Ippei Takahashi, Taku Obara, Akira Narita, Mami Ishikuro, Masatsugu Orui, Keiko Murakami, Aoi Noda, Genki Shinoda, Masato Takase, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Yuka Kotozaki, Atsushi Shimizu, Kozo Tanno, Atsushi Hozawa, Gen Tamiya, Naoki Kondo, Shinichi Kuriyama

    Translational psychiatry　16　(1)　2026/02/17

    DOI： 10.1038/s41398-026-03896-9 　

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    Social isolation, characterized by a lack of social connections with family, friends, and others, is associated with adverse health outcomes. However, the genetic contribution to the susceptibility to social isolation remains unclear. This study aimed to identify genetic loci associated with social isolation using the Lubben Social Network Scale (LSNS-6) in a Japanese population. The Tohoku Medical Megabank Community-Based Cohort Study was conducted between 2013 and 2016. The participants were genotyped using the Affymetrix Axiom Japonica Array. The LSNS-6 was used to assess familial and friend ties through six questions and social isolation statuses were defined using the total scale, family subscale, and friend subscale. Genome-wide association studies (GWASs) were conducted using a generalized linear mixed model, adjusting for age, sex, 10 genetic principal components and batch effects. In total, 63,497 participants who completed genotyping and the LSNS-6 were included. The mean age was 59.4 ± 11.9 years, and 41,126 (64.8%) were female. Significant genetic loci were identified in GWASs for the total scale (rs10736933 near ACADSB and HMX3) and friend subscale of LSNS-6 (rs1778366 near LINC02315 and LRFN5). This study provides the first genome-wide evidence of social isolation in the Japanese population, suggesting associations with ACADSB, HMX3, LINC02315, and LRFN5. These findings could enable personalized prevention and intervention for social isolation and related psychiatric disorders.

  16. 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.

  17. Inter-individual differentially methylated region-targeted EWAS reveals epigenetic signatures of early childhood adversity. International-journal

    Taira Mayanagi, Junko Yagi, Hideki Ohmomo, Manami Akasaka, Kentaro Fukumoto, Shusaku Chiba, Shohei Komaki, Atsushi Shimizu, Takehito Yanbe, Mare Uchide, Yasuhito Yoshioka, Kaori Ogawa, Chiho Ishikawa, Shiori Minabe, Jun Ito, Kanako Ono, Nozomi Kaneko, Kenji Sobue

    Epigenomics　1-12　2026/01/07

    DOI： 10.1080/17501911.2026.2613008 　

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    AIMS: Adverse childhood experiences (ACEs), especially in early life, can affect psychosocial development and increase lifelong risk for mental disorders. ACEs are also known to induce persistent epigenetic changes. This study aimed to explore ACE-associated DNA methylation signatures using an epigenome-wide association study (EWAS) targeting inter-individual differentially methylated regions (DMRs). METHODS: We developed a targeted capture probe system covering ~1.3 million CpG sites within inter-individual DMRs. This system was applied to salivary DNA from drug-naïve children aged 6-12 years with exposure to multiple early-life ACEs (n = 23) or who had no ACEs (n = 21). RESULTS: We identified 15 novel DMRs significantly associated with ACEs. A cluster of six CpG sites within an exon of the EIF4G2 gene showed consistently increased methylation in children with ACEs, with strong inter-site correlations. Enrichment analysis indicated that genes near these DMRs are involved in neurodevelopmental disorders, suggesting that early adversity may influence brain development through epigenetic mechanisms. CONCLUSION: Our findings suggest that early adversity may contribute to lasting epigenetic modifications in children. The identified DMRs may serve as noninvasive biomarkers for retrospective ACE assessment and provide insights into the biological embedding of early-life stress.

  18. Integration of polygenic risk score with measured blood pressure reveals hidden risks of cardiovascular disease mortality: A Japanese prospective cohort study. International-journal

    Hiroshi Okumiyama, Ryosuke Fujii, Mako Nagayoshi, Masahiro Nakatochi, Yoshiki Tsuboi, Koji Suzuki, Hiroaki Ikezaki, Takuma Furukawa, Rieko Okada, Shiroh Tanoue, Sadao Suzuki, Teruhide Koyama, Kiyonori Kuriki, Naoyuki Takashima, Takeshi Watanabe, Asahi Hishida, Yukihide Momozawa, Mika Yageta Sakurai, Atsushi Shimizu, Kenji Wakai, Keitaro Matsuo

    Hypertension research : official journal of the Japanese Society of Hypertension　2025/12/24

    DOI： 10.1038/s41440-025-02486-4 　

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    Although previous studies reported that BP PRS is associated with CVD, it is less explored whether BP PRS and BP are jointly associated with CVD, especially among non-European populations. Therefore, we examined joint associations of BP control and BP polygenic risk score (PRS) with CVD mortality in a Japanese population. Data were obtained from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, the multi-centered cohort study with 14 study areas throughout Japan. Of which, we analyzed ~35,000 Japanese individuals (Mean age: 55 years old, Men: 44%) with measured BP data (11,242 and 23,904 participants in subgroup #1 and #2). We developed PRS for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in each subgroup. Participants were followed up from the baseline survey (2005-2014) to the end of 2020. Not elevated BP was defined as SBP ≤ 140 mmHg or DBP ≤ 90 mmHg regardless of antihypertensive medications. During the follow-up period, a total of 381 CVD deaths were observed. Compared with not elevated BP, HRs (95% CI) of CVD mortality were 1.98 (1.37-2.88) for elevated SBP and 2.41 (1.66-3.49) for elevated DBP. Compared to not elevated BP in the lowest PRS tertile, HRs (95% CI) of CVD mortality in the highest PRS tertile were 2.28 (1.17-4.43) for SBP and 3.08 (1.61-5.91) for DBP even though BP was not elevated. These associations in the subgroup #1 were replicated in the subgroup #2. Our findings highlighted the importance of BP PRS to detect a hidden CVD risk strata in addition to laboratory BP measurements.

  19. Exploring novel blood-based DNA methylation biomarkers for alzheimer's disease via targeted sequencing of highly variable CpG sites. International-journal

    Hideki Ohmomo, Shohei Komaki, Shiori Minabe, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Makoto Sasaki, Atsushi Shimizu

    BMC research notes　18　(1)　350-350　2025/08/12

    DOI： 10.1186/s13104-025-07417-7 　

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    OBJECTIVE: Dementia, particularly Alzheimer’s disease (AD), continues to be a major public health concern due to population aging, yet minimally invasive biomarkers for early diagnosis have not been established. DNA methylation (DNAm) has recently attracted considerable attention as a promising biomarker. This study aimed to identify blood-based DNAm biomarkers for early detection of AD. RESULTS: We analysed blood-derived DNA from 48 patients with AD (from Biobank Japan) and 48 age- and sex-matched controls (from the Tohoku Medical Megabank Biobank) using Apolipoprotein ε type 4 (APOE)-associated genotype analysis and targeted-bisulfite sequencing. High-risk APOE genotypes were more frequent in AD patients (23/48, [47.9%]) than in controls (6/48, [12.5%]). A typical case-control and APOE genotype-stratified epigenome-wide association study (EWAS) did not identify any genome-wide significant CpG sites. Although the primary findings were negative, some top CpG sites appeared in both analyses, including loci on the Cell Adhesion Molecule 1 (CADM1), Tubulin alpha 1b (TUBA1B), and Exocyst complex component 2 (EXOC2) genes, which have previously been linked to AD-related pathways. The relatively early clinical stage and uncertainty of disease onset might have limited detection sensitivity. Longitudinal studies with refined staging and multi-omics integration might clarify the biomarker potential of blood DNAm in AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-025-07417-7.

  20. Genetic predisposition for immunoglobulin E production explains atopic risk in children: Tohoku Medical Megabank cohort study. International-journal

    Yoichi Sutoh, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Shohei Komaki, Shiori Minabe, Hideki Ohmomo, Kozo Tanno, Atsushi Hozawa, Naoki Nakaya, Aoi Noda, Masatsugu Orui, Mami Ishikuro, Taku Obara, Shinichi Kuriyama, Makoto Sasaki, Atsushi Shimizu

    American journal of human genetics　112　(8)　1852-1863　2025/08/07

    DOI： 10.1016/j.ajhg.2025.06.015 　

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    The atopic march lacks early identification methods for high-risk children. In this study, we assessed whether the risk of atopic diseases in infants could be predicted using a polygenic score (PGS) for total immunoglobulin E (IgE) levels. The PGS estimated using the polygenic model generated by PRS-CS was significantly correlated with log-transformed IgE levels (ρ = 0.200, p < 2.2 × 10-16). Assessment of the risk from birth to 2 years of age in a Japanese birth cohort (n = 17,154) applying the estimated PGS revealed significantly elevated incidence risk ratios in the highest PGS quintile (Q5) compared with those in the reference quintiles (Q1-Q3) for food allergy (1.51-fold; 95% confidence interval: 1.30-1.76), atopic dermatitis (1.30-fold; 1.12-1.51), and both conditions (1.88-fold; 1.46-2.43). These findings address critical gaps in allergy and PGS research among non-European populations, suggesting the contribution of genetic predisposition to IgE production in early-onset allergic diseases and supporting the use of PGS in early intervention.

  21. Evaluating sex-specific prediction models for colorectal cancer risk using a genome-wide polygenic risk score and lifestyle factors in a Japanese population. International-journal

    Shiori Nakano, Taiki Yamaji, Tsuyoshi Hachiya, Aya Kuchiba, Atsushi Shimizu, Norie Sawada, Manami Inoue, Shoichiro Tsugane, Motoki Iwasaki

    Cancer epidemiology　98　102878-102878　2025/07/16

    DOI： 10.1016/j.canep.2025.102878 　

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    BACKGROUND: The predictive performance of a colorectal cancer (CRC) risk prediction model incorporating genome-wide polygenic risk scores (PRSs) and lifestyle factors remains unclear in Asian populations. This study aimed to develop and evaluate the Asian-specific models using a Japanese population-based prospective study. METHODS: We derived 31 genome-wide PRSs using a genome-wide association study of CRC from the Biobank Japan and selected the best-performing PRS with the highest C-index in development case-cohort, including 200 incident cases. In evaluation case-cohort, including 693 incident cases, we assessed the discrimination accuracy (C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)) of lifestyle, PRS, and combined models using 5-fold cross-validation methods and estimated 10-year absolute risk. RESULTS: Of the 31 derived PRSs, the PRS aggregating 104,677 variant risks performed best in the development case-cohort. The men and women in the highest quintiles of the PRS had an approximately three-fold and two-fold higher risk of CRC, respectively, than those in the lowest in the evaluation case-cohort. Meanwhile, the association of lifestyle factors with CRC risk was observed only in men. Incorporating the PRS into a lifestyle model improved the C-index from 0.64 to 0.66 for men and from 0.61 to 0.63 for women. The IDI and NRI values supported this improvement. The 10-year absolute risk was 3.3 % and 1.6 % for high-risk men and women, respectively, and 0.5 % for both low-risk men and women. CONCLUSIONS: This study suggests that the CRC risk prediction model utilizing genome-wide PRS for Asians is valuable; however, further improvement is needed before clinical implementation.

  22. Integration of Digital Phenotyping and Genomics for Dry Eye Disease: Protocol for a Prospective Cohort Study

    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-e67862　2025/05/12

    Publisher: JMIR Publications Inc.

    DOI： 10.2196/67862 　

    eISSN： 1929-0748

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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

  23. Genome-wide association study of plasma amino acids and Mendelian randomization for cardiometabolic traits Peer-reviewed

    Ryota Toki, Sotaro Fushiki, Shun Kojima, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Sei Harada, Miho Iida, Aya Hirata, Naoko Miyagawa, Minako Matsumoto, Shun Edagawa, Atsuko Miyake, Kazuyo Kuwabara, Akiyoshi Hirayama, Masahiro Sugimoto, Asako Sato, Kaori Amano, Tomoyoshi Soga, Masaru Tomita, Kazuharu Arakawa, Kengo Kinoshita, Mika Sakurai-Yageta, Gen Tamiya, Hideki Ohmomo, Atsushi Shimizu, Tomonori Okamura, Toru Takebayashi

    Scientific Reports　15　(1)　2025/04/25

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-025-98992-z 　

    eISSN： 2045-2322

  24. Risk factors and prediction for pediatric obesity: current status and future perspectives.

    Shiori Minabe, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Shohei Komaki, Motoki Nakao, Hideki Ohmomo, Yutaka Hasegawa, Yasushi Ishigaki, Kozo Tanno, Makoto Sasaki, Atsushi Shimizu

    Endocrine journal　2025/04/09

    DOI： 10.1507/endocrj.EJ24-0724 　

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    Childhood obesity is a growing global health concern, contributing to numerous non-communicable diseases and long-term health complications. The prevalence of obesity in children and adolescents continues to rise, driven by complex interactions among various factors. The key risk factors include both environmental and genetic influences. Environmental factors include family elements like household conditions and lifestyle, while genetic factors refer to inherited predispositions. More recently, epigenetic factors have gained attention, focusing on chemical modifications such as DNA methylation that are influenced by the prenatal and early-life environment and may contribute to obesity risk. Unlike obesity in adults, the risk factors for obesity in children are largely dependent on their family environments rather than individual behaviors. For effective intervention, it is important to identify at-risk children and their families as early as possible after birth. Despite advances in machine learning, polygenic risk scores, and epigenomic markers-which show promise as being more accurate and comprehensive prediction methods-no risk prediction models are currently in clinical use. Achieving predictions with higher accuracy, external validation, and consideration of population-specific factors (e.g., ethnic variability) while avoiding bias or stigma in targeted interventions is needed for effective childhood obesity prevention. Herein, we summarize environmental, genetic, and epigenetic risk factors for childhood obesity and review the unique situations and regional factors in Japan, which are the focus of our study. Furthermore, we introduce the major advances in risk prediction models for childhood obesity.

  25. エピジェネティック・クロックによる生物学的年齢と身体活動の関連解析

    永田 雅俊, 小巻 翔平, 西田 裕一郎, 大桃 秀樹, 原 めぐみ, 田中 恵太郎, 清水 厚志

    日本衛生学雑誌　80　(Suppl.)　S217-S217　2025/03

    Publisher: (一社)日本衛生学会

    ISSN： 0021-5082

    eISSN： 1882-6482

  26. Study Profile of the Iwate PGS Assessment and Risk Communication (PARC) Study

    Akiko Yoshida, Tomoharu Tokutomi, Nobuhiro Suzumori, Akimune Fukushima, Yukiko Toya, Hideki Ohmomo, Kozo Tanno, Yoichi Sutoh, Yuka Kotozaki, Tsuyoshi Hachiya, Kazuki Kumada, Hisaaki Kudo, Atsushi Hasegawa, Mika Sakurai-Yageta, Akira Narita, Yohei Hamanaka, Satoshi Nagaie, Soichi Ogishima, Fuji Nagami, Yayoi Otsuka-Yamasaki, Shohei Komaki, Shiori Minabe, Koichi Asahi, Ryujin Endo, Yasushi Ishigaki, Masayuki Yamamoto, Atsushi Shimizu, Makoto Sasaki

    Journal of Epidemiology　2025

    Publisher: Japan Epidemiological Association

    DOI： 10.2188/jea.je20250078 　

    ISSN： 0917-5040

    eISSN： 1349-9092

  27. DNA Methylation Study in DOHaD Theory: A Perspective from the Tohoku Medical Megabank (TMM) Project

    MINABE Shiori, KOMAKI Shohei, OHMOMO Hideki, SHIMIZU Atsushi

    Developmental Origins of Health and Disease Research　12　(1)　5-10　2024/06/07

    Publisher: Japan Society for Developmental Origins of Health and Disease

    DOI： 10.51067/dohad.12.1_5 　

    ISSN： 2187-2562

    eISSN： 2187-2597

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    The Tohoku Medical Megabank (TMM) project advances DOHaD research, studying how prenatal and early postnatal environmental factors influence health via DNA methylation in adulthood. A correction method for cellular composition bias in DNA methylation analysis of newborn umbilical cord blood was established based on whole epigenome analysis of nucleated red blood cells from 15 newborns. The methylation status of 92 umbilical cord blood samples, excluding perinatal disease cases, has been analyzed, supporting predictions of fetal epigenetic alterations. The analyzed cord blood epigenomic information is available in the iMETHYL database. Furthermore, ongoing research on DNA methylation in 158 three-generation families and 60 sets of identical twins within the TMM cohort could elucidate DOHaD's molecular mechanisms and environmental transgenerational impacts on health.

  28. 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.

  29. GWAS meta-analysis of kidney function traits in Japanese populations.

    Asahi Hishida, Masahiro Nakatochi, Yoichi Sutoh, Shiori Nakano, Yukihide Momozawa, Akira Narita, Kozo Tanno, Atsushi Shimizu, Atsushi Hozawa, Kengo Kinoshita, Taiki Yamaji, Atsushi Goto, Mitsuhiko Noda, Norie Sawada, Hiroaki Ikezaki, Mako Nagayoshi, Megumi Hara, Sadao Suzuki, Teruhide Koyama, Chihaya Koriyama, Sakurako Katsuura-Kamano, Aya Kadota, Kiyonori Kuriki, Masayuki Yamamoto, Makoto Sasaki, Motoki Iwasaki, Keitaro Matsuo, Kenji Wakai

    Journal of epidemiology　2024/04/06

    DOI： 10.2188/jea.JE20230281 　

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    BACKGROUND: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. METHODS: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). RESULTS: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10-8), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. CONCLUSIONS: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

  30. 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 　

  31. DNA Methylation Reference Panel by Gestational Age in Umbilical Cord Blood.

    Hirotaka Hamada, Komaki Shohei, Ohmomo Hideki, Kuriyama Shinichi, Sugawara Junichi, Saito Masatoshi, Shimizu Atsushi

    REPRODUCTIVE SCIENCES　31　225A-225A　2024/03

    ISSN： 1933-7191

    eISSN： 1933-7205

  32. Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses. International-journal

    Kouya Shiraishi, Atsushi Takahashi, Yukihide Momozawa, Yataro Daigo, Syuzo Kaneko, Takahisa Kawaguchi, Hideo Kunitoh, Shingo Matsumoto, Hidehito Horinouchi, Akiteru Goto, Takayuki Honda, Kimihiro Shimizu, Masahiro Torasawa, Daisuke Takayanagi, Motonobu Saito, Akira Saito, Yuichiro Ohe, Shun-Ichi Watanabe, Koichi Goto, Masahiro Tsuboi, Katsuya Tsuchihara, Sadaaki Takata, Tomomi Aoi, Atsushi Takano, Masashi Kobayashi, Yohei Miyagi, Kazumi Tanaka, Hiroyuki Suzuki, Daichi Maeda, Takumi Yamaura, Maiko Matsuda, Yoko Shimada, Takaaki Mizuno, Hiromi Sakamoto, Teruhiko Yoshida, Yasushi Goto, Tatsuya Yoshida, Taiki Yamaji, Makoto Sonobe, Shinichi Toyooka, Kazue Yoneda, Katsuhiro Masago, Fumihiro Tanaka, Megumi Hara, Nobuo Fuse, Satoshi S Nishizuka, Noriko Motoi, Norie Sawada, Yuichiro Nishida, Kazuki Kumada, Kenji Takeuchi, Kozo Tanno, Yasushi Yatabe, Kuniko Sunami, Tomoyuki Hishida, Yasunari Miyazaki, Hidemi Ito, Mitsuhiro Amemiya, Hirohiko Totsuka, Haruhiko Nakayama, Tomoyuki Yokose, Kazuyoshi Ishigaki, Toshiteru Nagashima, Yoichi Ohtaki, Kazuhiro Imai, Ken Takasawa, Yoshihiro Minamiya, Kazuma Kobayashi, Kenichi Okubo, Kenji Wakai, Atsushi Shimizu, Masayuki Yamamoto, Motoki Iwasaki, Koichi Matsuda, Johji Inazawa, Yuichi Shiraishi, Hiroyoshi Nishikawa, Yoshinori Murakami, Michiaki Kubo, Fumihiko Matsuda, Yoichiro Kamatani, Ryuji Hamamoto, Keitaro Matsuo, Takashi Kohno

    Cancer communications (London, England)　44　(2)　287-293　2024/02

    DOI： 10.1002/cac2.12498 　

  33. Association between infertility treatment and hypertensive disorders of pregnancy in the Japan Birth Cohort Consortium: a meta-analysis. International-journal

    Mami Ishikuro, Tomoko Nishimura, Hiroyoshi Iwata, Hirohito Metoki, Taku Obara, Noriyuki Iwama, Keiko Murakami, Md Shafiur Rahman, Maki Tojo, Sumitaka Kobayashi, Chihiro Miyashita, Keiko Tanaka, Yoshihiro Miyake, Kazue Ishitsuka, Reiko Horikawa, Naho Morisaki, Midori Yamamoto, Kenichi Sakurai, Chisato Mori, Atsushi Shimizu, Fumihiro Sata, Kenji J Tsuchiya, Reiko Kishi, Shinichi Kuriyama

    Journal of human hypertension　38　(2)　187-190　2024/02

    DOI： 10.1038/s41371-023-00890-2 　

  34. Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people. International-journal

    Yuriko N Koyanagi, Masahiro Nakatochi, Shinichi Namba, Isao Oze, Hadrien Charvat, Akira Narita, Takahisa Kawaguchi, Hiroaki Ikezaki, Asahi Hishida, Megumi Hara, Toshiro Takezaki, Teruhide Koyama, Yohko Nakamura, Sadao Suzuki, Sakurako Katsuura-Kamano, Kiyonori Kuriki, Yasuyuki Nakamura, Kenji Takeuchi, Atsushi Hozawa, Kengo Kinoshita, Yoichi Sutoh, Kozo Tanno, Atsushi Shimizu, Hidemi Ito, Yumiko Kasugai, Yukino Kawakatsu, Yukari Taniyama, Masahiro Tajika, Yasuhiro Shimizu, Etsuji Suzuki, Yasuyuki Hosono, Issei Imoto, Yasuharu Tabara, Meiko Takahashi, Kazuya Setoh, Koichi Matsuda, Shiori Nakano, Atsushi Goto, Ryoko Katagiri, Taiki Yamaji, Norie Sawada, Shoichiro Tsugane, Kenji Wakai, Masayuki Yamamoto, Makoto Sasaki, Fumihiko Matsuda, Yukinori Okada, Motoki Iwasaki, Paul Brennan, Keitaro Matsuo

    Science advances　10　(4)　eade2780　2024/01/26

    DOI： 10.1126/sciadv.ade2780 　

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    An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

  35. Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS).

    Sei Harada, Miho Iida, Naoko Miyagawa, Aya Hirata, Kazuyo Kuwabara, Minako Matsumoto, Tomonori Okamura, Shun Edagawa, Yoko Kawada, Atsuko Miyake, Ryota Toki, Miki Akiyama, Atsuki Kawai, Daisuke Sugiyama, Yasunori Sato, Ryo Takemura, Kota Fukai, Yoshiki Ishibashi, Suzuka Kato, Ayako Kurihara, Mizuki Sata, Takuma Shibuki, Ayano Takeuchi, Shun Kohsaka, Mitsuaki Sawano, Satoshi Shoji, Yoshikane Izawa, Masahiro Katsumata, Koichi Oki, Shinichi Takahashi, Tsubasa Takizawa, Hiroshi Maruya, Yuji Nishiwaki, Ryo Kawasaki, Akiyoshi Hirayama, Takamasa Ishikawa, Rintaro Saito, Asako Sato, Tomoyoshi Soga, Masahiro Sugimoto, Masaru Tomita, Shohei Komaki, Hideki Ohmomo, Kanako Ono, Yayoi Otsuka-Yamasaki, Atsushi Shimizu, Yoichi Sutoh, Atsushi Hozawa, Kengo Kinoshita, Seizo Koshiba, Kazuki Kumada, Soichi Ogishima, Mika Sakurai-Yageta, Gen Tamiya, Toru Takebayashi

    Journal of epidemiology　2024/01/06

    DOI： 10.2188/jea.JE20230192 　

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    The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

  36. Association between vascular endothelial dysfunction and stroke incidence in the general Japanese population: Results from the tohoku medical megabank community-based cohort study

    Harutomo Numazaki, Takahito Nasu, Mamoru Satoh, Yuka Kotozaki, Kozo Tanno, Koichi Asahi, Hideki Ohmomo, Atsushi Shimizu, Shinichi Omama, Yoshihiro Morino, Kenji Sobue, Makoto Sasaki

    International Journal of Cardiology Cardiovascular Risk and Prevention　19　200216-200216　2023/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.ijcrp.2023.200216 　

    ISSN： 2772-4875

  37. Metabolomics profiles alterations in cigarette smokers and heated tobacco product users. Peer-reviewed

    Sei Harada, Hideki Ohmomo, Minako Matsumoto, Mizuki Sata, Miho Iida, Aya Hirata, Naoko Miyagawa, Kazuyo Kuwabara, Suzuka Kato, Ryota Toki, Shun Edagawa, Daisuke Sugiyama, Asako Sato, Akiyoshi Hirayama, Masahiro Sugimoto, Tomoyoshi Soga, Masaru Tomita, Atsushi Shimizu, Tomonori Okamura, Toru Takebayashi

    Journal of epidemiology　2023/11/04

    DOI： 10.2188/jea.JE20230170 　

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    BACKGROUND: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment. METHODS: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey. RESULTS: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels. CONCLUSIONS: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

  38. 肥満者と非肥満者におけるウエスト周囲長に関連するライフスタイルの解析

    武部 典子, 長谷川 豊, 丹野 高三, 大桃 秀樹, 清水 厚志, 岡田 健太, 佐々木 真理, 石垣 泰

    肥満研究　29　(合同学術集会抄録集)　313-313　2023/11

    Publisher: (一社)日本肥満学会

    ISSN： 1343-229X

  39. jMorp: Japanese Multi-Omics Reference Panel update report 2023. International-journal

    Shu Tadaka, Junko Kawashima, Eiji Hishinuma, Sakae Saito, Yasunobu Okamura, Akihito Otsuki, Kaname Kojima, Shohei Komaki, Yuichi Aoki, Takanari Kanno, Daisuke Saigusa, Jin Inoue, Matsuyuki Shirota, Jun Takayama, Fumiki Katsuoka, Atsushi Shimizu, Gen Tamiya, Ritsuko Shimizu, Masahiro Hiratsuka, Ikuko N Motoike, Seizo Koshiba, Makoto Sasaki, Masayuki Yamamoto, Kengo Kinoshita

    Nucleic acids research　2023/11/01

    DOI： 10.1093/nar/gkad978 　

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    Modern medicine is increasingly focused on personalized medicine, and multi-omics data is crucial in understanding biological phenomena and disease mechanisms. Each ethnic group has its unique genetic background with specific genomic variations influencing disease risk and drug response. Therefore, multi-omics data from specific ethnic populations are essential for the effective implementation of personalized medicine. Various prospective cohort studies, such as the UK Biobank, All of Us and Lifelines, have been conducted worldwide. The Tohoku Medical Megabank project was initiated after the Great East Japan Earthquake in 2011. It collects biological specimens and conducts genome and omics analyses to build a basis for personalized medicine. Summary statistical data from these analyses are available in the jMorp web database (https://jmorp.megabank.tohoku.ac.jp), which provides a multidimensional approach to the diversity of the Japanese population. jMorp was launched in 2015 as a public database for plasma metabolome and proteome analyses and has been continuously updated. The current update will significantly expand the scale of the data (metabolome, genome, transcriptome, and metagenome). In addition, the user interface and backend server implementations were rewritten to improve the connectivity between the items stored in jMorp. This paper provides an overview of the new version of the jMorp.

  40. Integrated analysis of human DNA methylation, gene expression, and genomic variation in iMETHYL database using kernel tensor decomposition-based unsupervised feature extraction

    Y-h. Taguchi, Shohei Komaki, Yoichi Sutoh, Hideki Ohmomo, Yayoi Otsuka-Yamasaki, Atsushi Shimizu

    PLOS ONE　18　(8)　e0289029-e0289029　2023/08/09

    Publisher: Public Library of Science (PLoS)

    DOI： 10.1371/journal.pone.0289029 　

    eISSN： 1932-6203

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    Integrating gene expression, DNA methylation, and genomic variants simultaneously without location coincidence (i.e., irrespective of distance from each other) or pairwise coincidence (i.e., direct identification of triplets of gene expression, DNA methylation, and genomic variants, and not integration of pairwise coincidences) is difficult. In this study, we integrated gene expression, DNA methylation, and genome variants from the iMETHYL database using the recently proposed kernel tensor decomposition-based unsupervised feature extraction method with limited computational resources (i.e., short CPU time and small memory requirements). Our methods do not require prior knowledge of the subjects because they are fully unsupervised in that unsupervised tensor decomposition is used. The selected genes and genomic variants were significantly targeted by transcription factors that were biologically enriched in KEGG pathway terms as well as in the intra-related regulatory network. The proposed method is promising for integrated analyses of gene expression, methylation, and genomic variants with limited computational resources.

  41. 新生児臍帯血の網羅的エピゲノム解析による妊娠初期までの喫煙経験が次世代に及ぼす影響

    美辺 詩織, 小巻 翔平, 大桃 秀樹, 高嶋 聰, 小野 加奈子, 山崎 弥生, 須藤 洋一, 田高 周, 水野 聖士, 石黒 真美, 工藤 久智, 小原 拓, 熊田 和貴, 勝岡 史城, 荻島 創一, 木下 賢吾, 菅原 準一, 栗山 進一, 清水 厚志

    DOHaD研究　11　(3)　37-37　2023/08

    Publisher: (一社)日本DOHaD学会

    ISSN： 2187-2562

    eISSN： 2187-2597

  42. 地域住民コホートにおける脈波伝播速度(PWV)と生活習慣の関係

    武部 典子, 長谷川 豊, 大桃 秀樹, 清水 厚志, 丹野 高三, 旭 浩一, 岡田 健太, 佐々木 真理, 石垣 泰

    日本動脈硬化学会総会プログラム・抄録集　55回　275-275　2023/06

    Publisher: (一社)日本動脈硬化学会

    ISSN： 1347-7099

  43. 日本人に最適化した新規エピゲノムクロックの開発

    清水 厚志, 小巻 翔平, 永田 雅俊, 大友 亮, 小野 加奈子, 大桃 秀樹, 梅影 創, 篠崎 夏子, 八谷 剛史, 須藤 洋一, 山崎 弥生, 米山 暁夫, 佐々木 真理

    日本抗加齢医学会総会プログラム・抄録集　23回　210-210　2023/06

    Publisher: (一社)日本抗加齢医学会

  44. 長寿者のエピゲノム解析

    小巻 翔平, 永田 雅俊, 新井 恵吏, 大友 亮, 小野 加奈子, 阿部 由紀子, 大桃 秀樹, 梅影 創, 篠崎 夏子, 八谷 剛史, 須藤 洋一, 山崎 弥生[大塚], 新井 康通, 広瀬 信義, 米山 暁夫, 岡野 栄之, 佐々木 真理, 金井 弥栄, 清水 厚志

    日本抗加齢医学会総会プログラム・抄録集　23回　220-220　2023/06

    Publisher: (一社)日本抗加齢医学会

  45. 出生三世代コホートにおける7人家族のエピゲノム研究基盤構築

    美辺 詩織, 小巻 翔平, 大桃 秀樹, 高嶋 聰, 小野 加奈子, 山崎 弥生, 須藤 洋一, 田高 周, 水野 聖士, 石黒 真美, 工藤 久智, 小原 拓, 熊田 和貴, 勝岡 史城, 荻島 創一, 木下 賢吾, 菅原 準一, 栗山 進一, 清水 厚志

    日本抗加齢医学会総会プログラム・抄録集　23回　252-252　2023/06

    Publisher: (一社)日本抗加齢医学会

  46. Investigating the association between glycaemic traits and colorectal cancer in the Japanese population using Mendelian randomisation. International-journal

    Akiko Hanyuda, Atsushi Goto, Ryoko Katagiri, Yuriko N Koyanagi, Masahiro Nakatochi, Yoichi Sutoh, Shiori Nakano, Isao Oze, Hidemi Ito, Taiki Yamaji, Norie Sawada, Masao Iwagami, Aya Kadota, Teruhide Koyama, Sakurako Katsuura-Kamano, Hiroaki Ikezaki, Keitaro Tanaka, Toshiro Takezaki, Issei Imoto, Midori Suzuki, Yukihide Momozawa, Kenji Takeuchi, Akira Narita, Atsushi Hozawa, Kengo Kinoshita, Atsushi Shimizu, Kozo Tanno, Keitaro Matsuo, Shoichiro Tsugane, Kenji Wakai, Makoto Sasaki, Masayuki Yamamoto, Motoki Iwasaki

    Scientific reports　13　(1)　7052-7052　2023/04/29

    DOI： 10.1038/s41598-023-33966-7 　

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    Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated fasting glucose, haemoglobin A1c (HbA1c), and fasting C-peptide and colorectal cancer risk. In the single nucleotide polymorphism (SNP)-exposure analysis, we meta-analysed study-level genome-wide associations of fasting glucose (~ 17,289 individuals), HbA1c (~ 52,802 individuals), and fasting C-peptide (1,666 individuals) levels from the Japanese Consortium of Genetic Epidemiology studies. The odds ratios of colorectal cancer were 1.01 (95% confidence interval [CI], 0.99-1.04, P = 0.34) for fasting glucose (per 1 mg/dL increment), 1.02 (95% CI, 0.60-1.73, P = 0.95) for HbA1c (per 1% increment), and 1.47 (95% CI, 0.97-2.24, P = 0.06) for fasting C-peptide (per 1 log increment). Sensitivity analyses, including Mendelian randomisation-Egger and weighted-median approaches, revealed no significant association between glycaemic characteristics and colorectal cancer (P > 0.20). In this study, genetically predicted glycaemic characteristics were not significantly related to colorectal cancer risk. The potential association between insulin resistance and colorectal cancer should be validated in further studies.

  47. 日本人集団におけるメタボロームGWAS(mGWAS)の解析手順の検討

    土岐 了大, 小島 駿, 伏木 蒼太郎, 原田 成, 平田 あや, 飯田 美穂, 宮川 尚子, 枝川 峻, 須藤 洋一, 大桃 秀樹, 山崎 弥生, 清水 厚志, 武林 亨

    日本衛生学雑誌　78　(Suppl.)　S192-S192　2023/03

    Publisher: (一社)日本衛生学会

    ISSN： 0021-5082

    eISSN： 1882-6482

  48. 日本人集団におけるメタボロームGWAS(mGWAS)の解析手順の検討

    土岐 了大, 小島 駿, 伏木 蒼太郎, 原田 成, 平田 あや, 飯田 美穂, 宮川 尚子, 枝川 峻, 須藤 洋一, 大桃 秀樹, 山崎 弥生, 清水 厚志, 武林 亨

    日本衛生学雑誌　78　(Suppl.)　S192-S192　2023/03

    Publisher: (一社)日本衛生学会

    ISSN： 0021-5082

    eISSN： 1882-6482

  49. Development and validation of genome-wide polygenic risk scores for predicting breast cancer incidence in Japanese females: a population-based case-cohort study. International-journal

    Hiroyuki Ohbe, Tsuyoshi Hachiya, Taiki Yamaji, Shiori Nakano, Yoshihisa Miyamoto, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Atsushi Shimizu, Hideo Yasunaga, Norie Sawada, Manami Inoue, Shoichiro Tsugane, Motoki Iwasaki

    Breast cancer research and treatment　197　(3)　661-671　2023/02

    DOI： 10.1007/s10549-022-06843-6 　

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    PURPOSE: This study aimed to develop an ancestry-specific polygenic risk scores (PRSs) for the prediction of breast cancer events in Japanese females and validate it in a longitudinal cohort study. METHODS: Using publicly available summary statistics of female breast cancer genome-wide association study (GWAS) of Japanese and European ancestries, we, respectively, developed 31 candidate genome-wide PRSs using pruning and thresholding (P + T) and LDpred methods with varying parameters. Among the candidate PRS models, the best model was selected using a case-cohort dataset (63 breast cancer cases and 2213 sub-cohorts of Japanese females during a median follow-up of 11.9 years) according to the maximal predictive ability by Harrell's C-statistics. The best-performing PRS for each derivation GWAS was evaluated in another independent case-cohort dataset (260 breast cancer cases and 7845 sub-cohorts of Japanese females during a median follow-up of 16.9 years). RESULTS: For the best PRS model involving 46,861 single nucleotide polymorphisms (SNPs; P + T method with PT = 0.05 and R2 = 0.2) derived from Japanese-ancestry GWAS, the Harrell's C-statistic was 0.598 ± 0.018 in the evaluation dataset. The age-adjusted hazard ratio for breast cancer in females with the highest PRS quintile compared with those in the lowest PRS quintile was 2.47 (95% confidence intervals, 1.64-3.70). The PRS constructed using Japanese-ancestry GWAS demonstrated better predictive performance for breast cancer in Japanese females than that using European-ancestry GWAS (Harrell's C-statistics 0.598 versus 0.586). CONCLUSION: This study developed a breast cancer PRS for Japanese females and demonstrated the usefulness of the PRS for breast cancer risk stratification.

  50. Anti-Helicobacter pylori antibody status is associated with cancer mortality: A longitudinal analysis from the Japanese DAIKO prospective cohort study. International-journal

    Satoshi S Nishizuka, Masahiro Nakatochi, Yuka Koizumi, Asahi Hishida, Rieko Okada, Sayo Kawai, Yoichi Sutoh, Keisuke Koeda, Atsushi Shimizu, Mariko Naito, Kenji Wakai

    PLOS global public health　3　(2)　e0001125　2023

    DOI： 10.1371/journal.pgph.0001125 　

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    Paradoxically, patients with advanced stomach cancer who are Helicobacter pylori-positive (HP+) have a higher survival rate than those who are HP-. This finding suggests that HP infection has beneficial effects for cancer treatment. The present study examines whether HP+ individuals have a lower likelihood of death from cancer than those who are HP-. Prospective cohort data (n = 4,982 subjects enrolled in the DAIKO study between 2008-2010) were used to assess whether anti-HP antibody status was associated with cancer incidence. The median age in the primary registry was 53 years-old (range 35-69 years-old). Over the 8-year observation period there were 234 (4.7%) cancer cases in the cohort and 88 (1.8%) all-cause deaths. Urine anti-HP antibody data was available for all but one participant (n = 4,981; 99.98%). The number of HP+ and HP- individuals was 1,825 (37%) and 3,156 (63%), respectively. Anti-HP antibody distribution per birth year revealed that earlier birth year was associated with higher HP+ rates. With a birth year-matched cohort (n = 3,376), all-cancer incidence was significantly higher in HP+ individuals than those who were HP- (p = 0.00328), whereas there was no significant difference in the cancer death rate between HP+ and HP- individuals (p = 0.888). Cox regression analysis for prognostic factors revealed that the hazards ratio of HP+ was 1.59-fold (95%CI 1.17-2.26) higher than HP- in all-cancer incidence. Potential systemic effects of HP+ status may contribute to reduced likelihood of death for patients after an initial diagnosis of cancer.

  51. Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population

    Takuya Sakashita, Yasuyuki Nakamura, Yoichi Sutoh, Atsushi Shimizu, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Naoyuki Takashima, Aya Kadota, Katsuyuki Miura, Yoshikuni Kita, Hiroaki Ikezaki, Jun Otonari, Keitaro Tanaka, Chisato Shimanoe, Teruhide Koyama, Isao Watanabe, Sadao Suzuki, Hiroko Nakagawa-Senda, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Rieko Okada, Kiyonori Kuriki, Sakurako Katsuura-Kamano, Takeshi Watanabe, Shiroh Tanoue, Chihaya Koriyama, Isao Oze, Yuriko N. Koyanagi, Yohko Nakamura, Miho Kusakabe, Masahiro Nakatochi, Yukihide Momozawa, Kenji Wakai, Keitaro Matsuo

    Diabetology International　14　(2)　188-198　2023

    DOI： 10.1007/s13340-023-00618-0 　

    ISSN： 2190-1678

    eISSN： 2190-1686

  52. Association between plasma xanthine oxidoreductase activity and the renal function in a general Japanese population: The Tohoku Medical Megabank community-based cohort study. International-journal

    Satoru Taguchi, Takahito Nasu, Mamoru Satoh, Yuka Kotozaki, Kozo Tanno, Fumitaka Tanaka, Koichi Asahi, Hideki Ohmomo, Hiroto Kikuchi, Takamasa Kobayashi, Yoshihiro Morino, Atsushi Shimizu, Kenji Sobue, Makoto Sasaki

    Kidney & blood pressure research　2022/11/01

    DOI： 10.1159/000527654 　

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    INTRODUCTION: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population. METHODS: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture. Chronic kidney disease (CKD) was estimated using the estimated glomerular filtration rate of cystatin C (eGFRcys). Individuals with a history of hyperuricemia or severe renal dysfunction (eGFRcys < 15 ml/min/1.73 m2 or undergoing dialysis) were excluded from the study. We performed a multinominal multivariate logistic analysis adjusted for age, blood pressure, uric acid, glycated hemoglobin A1c, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to associate XOR activity and renal function. RESULTS: The present study included 4,248 participants (male/female: 1,373/2,875, age: 62.9 ± 11.7 years). When participants were divided according to XOR quartiles, blood pressure, body mass index, uric acid, low-density lipoprotein cholesterol and glycated hemoglobin A1c were highest in the highest XOR quartile (all p < 0.001). The XOR activity was significantly higher in the subgroup with CKD stage G3 and G4 (G1 vs. G2 vs. G3-G4: 44.8 ± 40.5 vs 52.0 ± 42.9 vs. 54.1 ± 43.9 pmol / h / mL, p = 0.02). The higher XOR activity was significantly associated with an increase of CKD stage: the odd ratios (95% confidence intervals) per 1 pmol/h/mL increase in XOR activity with CKD stage G1 as a reference were 1.37 (1.13-1.73) in G2 and 1.51 (1.30-1.84) in G3-G4. CONCLUSION: The present study concluded that high XOR activity was associated with the severity of CKD in a general Japanese population, suggesting that upregulated XOR activity may be involved in advanced renal dysfunction.

  53. Association between high-sensitivity cardiac troponin T levels and incident stroke in the elderly Japanese population: Results from the Tohoku Medical Megabank Community-based Cohort Study

    Takamasa Kobayashi, Takahito Nasu, Mamoru Satoh, Yuka Kotozaki, Kozo Tanno, Koichi Asahi, Hideki Ohmomo, Atsushi Shimizu, Shinichi Omama, Hiroto Kikuchi, Satoru Taguchi, Yoshihiro Morino, Kenji Sobue, Makoto Sasaki

    American Heart Journal Plus: Cardiology Research and Practice　22　100212-100212　2022/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.ahjo.2022.100212 　

    ISSN： 2666-6022

  54. Association between glycemic traits and primary open-angle glaucoma: A Mendelian randomization study in the Japanese population. International-journal

    Akiko Hanyuda, Atsushi Goto, Masahiro Nakatochi, Yoichi Sutoh, Akira Narita, Shiori Nakano, Ryoko Katagiri, Kenji Wakai, Naoyuki Takashima, Teruhide Koyama, Kokichi Arisawa, Issei Imoto, Yukihide Momozawa, Kozo Tanno, Atsushi Shimizu, Atsushi Hozawa, Kengo Kinoshita, Taiki Yamaji, Norie Sawada, Masao Iwagami, Kenya Yuki, Kazuo Tsubota, Kazuno Negishi, Keitaro Matsuo, Masayuki Yamamoto, Makoto Sasaki, Shoichiro Tsugane, Motoki Iwasaki

    American journal of ophthalmology　245　193-201　2022/09/23

    DOI： 10.1016/j.ajo.2022.09.004 　

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    PURPOSE: A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of POAG. DESIGN: Two-sample MR design. METHODS: We examined the genetically predicted measures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP)-exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n=17,289; n of SNPs=34), HbA1c (n=52,802; n of SNPs=43), and fasting C-peptide levels (n=1,666; n of SNPs=17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n=3,980 POAG cases and 18,815 controls) for the SNP-outcome association. RESULTS: We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P=0.25) for HbA1c (per 1 % increment) and 0.92 (95% CI, 0.56-1.53; P=0.76) for fasting C-peptide (per two-fold increment). A significant association between fasting glucose (per 10 mg/dL increment) and POAG was observed according to the MR IVW analysis (OR=1.48 [95% CI, 1.10-1.79, P=0.009]); however, sensitivity analyses, including MR-Egger and weighted-median methods, did not support this association (P>0.10). CONCLUSIONS: We did not provide strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.

  55. 全血由来DNAにおけるエピゲノム関連解析による淡明細胞型腎細胞がんの検出に有用なDNAメチル化バイオマーカー候補の同定(Potential DNA methylation biomarkers for ccRCC identified by a whole blood-based epigenome-wide association study)

    大桃 秀樹, 新井 恵吏, 吉田 輝彦, 金井 弥栄, 清水 厚志

    日本癌学会総会記事　81回　P-1088　2022/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  56. Blood lipids and the risk of colorectal cancer: Mendelian randomization analyses in the Japanese Consortium of Genetic Epidemiology studies. International-journal

    Masao Iwagami, Atsushi Goto, Ryoko Katagiri, Yoichi Sutoh, Yuriko N Koyanagi, Masahiro Nakatochi, Shiori Nakano, Akiko Hanyuda, Akira Narita, Atsushi Shimizu, Kozo Tanno, Atsushi Hozawa, Kengo Kinoshita, Isao Oze, Hidemi Ito, Taiki Yamaji, Norie Sawada, Yohko Nakamura, Sho Nakamura, Kiyonori Kuriki, Sadao Suzuki, Asahi Hishida, Yumiko Kasugai, Issei Imoto, Midori Suzuki, Yukihide Momozawa, Kenji Takeuchi, Masayuki Yamamoto, Makoto Sasaki, Keitaro Matsuo, Shoichiro Tsugane, Kenji Wakai, Motoki Iwasaki

    Cancer prevention research (Philadelphia, Pa.)　15　(12)　827-836　2022/08/30

    DOI： 10.1158/1940-6207.CAPR-22-0146 　

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    The associations between blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), and colorectal cancer risk are controversial. We evaluated potential causal relationships between blood lipids and colorectal cancer risk. Using the baseline data from the Japanese Consortium of Genetic Epidemiology studies, we estimated the single-nucleotide polymorphism (SNP)-exposure associations (n=34,546 for TC, n=50,290 for HDL-C, n=51,307 for triglycerides, and n=30,305 for LDL-C). We also estimated the SNP-outcome associations in another Japanese dataset (n=7,936 colorectal cancer cases and n=38,042 controls). We conducted Mendelian randomization analyses for the association between each blood lipid type and the risk of colorectal cancer using an inverse variance-weighted method. The total variances explained by the selected SNPs in TC (68 SNPs), HDL-C (50 SNPs), log-transformed triglycerides (26 SNPs), and LDL-C (35 SNPs) were 7.0%, 10.0%, 6.2%, and 5.7%, respectively. The odds ratios for colorectal cancer were 1.15 (95% confidence interval 1.01-1.32) per 1 standard deviation (SD) (33.3 mg/dL) increase in TC, 1.11 (0.98-1.26) per 1 SD (15.4 mg/dL) increase in HDL-C, 1.06 (0.90-1.26) per 1 SD (0.5 log-mg/dL) increase in log-transformed triglycerides, and 1.17 (0.91-1.50) per 1 SD (29.6 mg/dL) increase in LDL-C. Sensitivity analyses consistently suggested the positive association between TC and colorectal cancer, whereas results of each lipid component were inconsistent. In conclusion, this large Mendelian randomization study of a Japanese population showed a potentially causal association between high TC and colorectal cancer risk, although the association between each lipid component and colorectal cancer remained inconclusive.

  57. Association between total type I collagen N-terminal propeptide and coronary artery disease risk score in the general Japanese population. International-journal

    Hiroto Kikuchi, Takahito Nasu, Mamoru Satoh, Yuka Kotozaki, Kozo Tanno, Koichi Asahi, Hideki Ohmomo, Takamasa Kobayashi, Satoru Taguchi, Yoshihiro Morino, Atsushi Shimizu, Kenji Sobue, Makoto Sasaki

    International journal of cardiology. Heart & vasculature　41　101056-101056　2022/08

    DOI： 10.1016/j.ijcha.2022.101056 　

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    Background: Bone metabolic dysregulation plays an important role in the pathogenesis of atherosclerosis; however, whether its markers contribute to coronary artery disease (CAD) risk in the general population remains unclear. Therefore, this study aimed to analyze the association between bone metabolic markers and CAD risk score in the general Japanese population. Methods: The Iwate Medical Megabank Organization collected individual participant data during a community-based cohort study in the Iwate prefecture (n = 5,095, age = 58.9 ± 12.4 years). Participants with osteoporosis, chronic kidney disease, malignant disease, or primary wasting disease were excluded from the study. The present study measured the levels of circulating bone metabolic markers, including total type I collagen N-terminal propeptide (TP1NP), bone-type alkaline phosphatase, cross-linked N-telopeptide of type 1 collagen (NTX), and intact parathyroid hormone. CAD risk and atherosclerosis were evaluated using the Suita score and brachial-ankle pulse wave velocity (baPWV) measurement, respectively. Results: Among the bone metabolic markers, TP1NP was strongly associated with a high Suita score (≥56 points) (OR = 0.77, 95% CI = 0.69-0.82, P < 0.001). When participants were divided into quartiles of TP1NP levels, the subgroup with the lowest TP1NP level was associated with a high Suita score (≥56 points) and high baPWV (>1,400 cm/s). Conclusions: This study demonstrated that TP1NP levels decreased in participants with high Suita scores and high baPWV, suggesting that TP1NP downregulation may indicate future CAD risk and atherosclerosis progression in the general Japanese population.

  58. Epigenome-wide Association Study Identified VTI1A DNA Methylation Associated with Accelerometer-assessed Physical Activity. International-journal

    Yuichiro Nishida, Megumi Hara, Hideki Ohmomo, Kanako Ono, Atsushi Shimizu, Mikako Horita, Chisato Shimanoe, Naoto Taguchi, Yasuki Higaki, Keitaro Tanaka

    Medicine and science in sports and exercise　54　(11)　1879-1888　2022/06/11

    DOI： 10.1249/MSS.0000000000002970 　

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    INTRODUCTION: Health benefits of physical activity (PA) may be mediated by DNA methylation alterations. The purpose of the current study was to comprehensively identify CpG sites whose methylation levels were associated with accelerometer-assessed total PA in a general Japanese population. METHODS: The study participants were from the baseline survey of Saga Japan Multi-institutional Collaborative Cohort. PA was objectively measured by a single-axis accelerometer for seven days. We employed a two-stage strategy. In the discovery stage, we performed a meta-analysis of two epigenome-wide association studies (EWAS) of total PA in 898 individuals (a combination of random sample [n = 507] and case-control study sample [n = 391]. Peripheral blood DNA methylation levels were measured using Infinium EPIC or HM450 arrays. In the replication stage, we subsequently examined whether CpG sites significantly associated (P < 1 × 10-5) with total PA were replicated in another sample (n = 1711), in which methylation levels were measured by pyrosequencing. A multiple linear regression was performed to determine the cross-sectional association between total PA and methylation levels with adjustment for potential confounders, including BMI. A fixed-effects model was used in the meta-analysis. Correlations between total PA-associated DNA methylation and several inflammatory markers, such as hs-CRP, were also conducted. RESULTS: In the meta-analysis, nine CpG sites were significantly associated with total PA (P < 1 × 10-5). Among the nine sites, one site cg07030336 (annotated to VTI1A/ZDHHC6 gene) was successfully replicated (P = 0.009). CONCLUSIONS: The current study showed that greater accelerometer-assessed total PA was associated with higher DNA methylation levels at cg07030336 (VTI1A/ZDHHC6) in the general population. Additionally, we found a divergent relationship between the methylation levels at cg07030336 and several inflammatory biomarkers.

  59. Association between Social Isolation and Total Mortality after the Great East Japan Earthquake in Iwate Prefecture: Findings from the TMM CommCohort Study. International-journal

    Yuka Kotozaki, Kozo Tanno, Kiyomi Sakata, Kotaro Otsuka, Ryohei Sasaki, Nobuyuki Takanashi, Mamoru Satoh, Atsushi Shimizu, Makoto Sasaki

    International journal of environmental research and public health　19　(7)　2022/04/05

    DOI： 10.3390/ijerph19074343 　

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    This study aimed to investigate whether social isolation is associated with mortality, together with the effect of the Great East Japan Earthquake on mortality, due to the social isolation of community residents living in the affected areas, using data from the Tohoku Medical Megabank Project Community-Based Cohort Study. A total of 22,933 participants (8059 men and 14,874 women), who were free from cancer and cardiovascular disease, were followed up with death as an endpoint for five years. Social isolation was assessed using the Lubben Social Network Scale (cut-off, 11/12). Using Cox proportional hazards models, hazard ratios (HRs) of total mortality and 95% confidence intervals (CIs) associated with social isolation (no isolation as the reference) were estimated. The latter was significantly associated with an increased risk of total mortality (1.38 (1.04-1.83) in men and 1.49 (1.02-2.19) in women). Moreover, among those with social isolation, the risk of mortality was significantly higher, especially for women with house damage and men who had experienced a death in the family. The disaster may have raised the risk of mortality due to social isolation.

  60. 地域住民コホートにおける脈波伝播速度(PWV)と心血管疾患リスクスコア、生活習慣の関係

    武部 典子, 丹野 高三, 大桃 秀樹, 半谷 真理, 長谷川 豊, 清水 厚志, 坂田 清美, 佐々木 真理, 石垣 泰

    糖尿病　65　(Suppl.1)　S-187　2022/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  61. Resistance to chemical carcinogenesis induction via a dampened inflammatory response in naked mole-rats. International-journal

    Kaori Oka, Shusuke Fujioka, Yoshimi Kawamura, Yoshihiro Komohara, Takeshi Chujo, Koki Sekiguchi, Yuki Yamamura, Yuki Oiwa, Natsuko Omamiuda-Ishikawa, Shohei Komaki, Yoichi Sutoh, Satoko Sakurai, Kazuhito Tomizawa, Hidemasa Bono, Atsushi Shimizu, Kimi Araki, Takuya Yamamoto, Yasuhiro Yamada, Hiroyuki Oshiumi, Kyoko Miura

    Communications biology　5　(1)　287-287　2022/03/30

    DOI： 10.1038/s42003-022-03241-y 　

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    Naked mole-rats (NMRs) have a very low spontaneous carcinogenesis rate, which has prompted studies on the responsible mechanisms to provide clues for human cancer prevention. However, it remains unknown whether and how NMR tissues respond to experimental carcinogenesis induction. Here, we show that NMRs exhibit extraordinary resistance against potent chemical carcinogenesis induction through a dampened inflammatory response. Although carcinogenic insults damaged skin cells of both NMRs and mice, NMR skin showed markedly lower immune cell infiltration. NMRs harbour loss-of-function mutations in RIPK3 and MLKL genes, which are essential for necroptosis, a type of necrotic cell death that activates strong inflammation. In mice, disruption of Ripk3 reduced immune cell infiltration and delayed carcinogenesis. Therefore, necroptosis deficiency may serve as a cancer resistance mechanism via attenuating the inflammatory response in NMRs. Our study sheds light on the importance of a dampened inflammatory response as a non-cell-autonomous cancer resistance mechanism in NMRs.

  62. A genome-wide association study on adherence to low-carbohydrate diets in Japanese. International-journal

    Yasuyuki Nakamura, Takashi Tamura, Akira Narita, Atsushi Shimizu, Yoichi Sutoh, Naoyuki Takashima, Kenji Matsui, Naoko Miyagawa, Aya Kadota, Katsuyuki Miura, Jun Otonari, Hiroaki Ikezaki, Asahi Hishida, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Keitaro Tanaka, Chisato Shimanoe, Rie Ibusuki, Daisaku Nishimoto, Isao Oze, Hidemi Ito, Etsuko Ozaki, Daisuke Matsui, Haruo Mikami, Miho Kusakabe, Sadao Suzuki, Miki Watanabe, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kiyonori Kuriki, Masahiro Nakatochi, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Kenji Wakai

    European journal of clinical nutrition　76　(8)　1103-1110　2022/02/07

    DOI： 10.1038/s41430-022-01090-w 　

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    BACKGROUND/OBJECTIVES: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown. SUBJECTS/METHODS: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables. RESULTS: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10-8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score. CONCLUSION: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.

  63. Public Access to Summary Statistics for Genome-wide Association Studies of Body Mass Index, Weight, and Height Among Healthy Japanese Individuals: The Japanese Consortium of Genetic Epidemiology Studies.

    Atsushi Goto, Shiori Suzuki, Ryoko Katagiri, Taiki Yamaji, Norie Sawada, Masahiro Nakatochi, Kenji Wakai, Atsushi Hozawa, Kengo Kinoshita, Kozo Tanno, Atsushi Shimizu, Hidemi Ito, Keitaro Matsuo, Motoki Iwasaki

    Journal of epidemiology　32　(2)　115-116　2022/02/05

    DOI： 10.2188/jea.JE20210459 　

  64. Low MICA Gene Expression Confers an Increased Risk of Graves' Disease: A Mendelian Randomization Study. International-journal

    Yoichi Sutoh, Shohei Komaki, Taiki Yamaji, Shiori Suzuki, Ryoko Katagiri, Norie Sawada, Kanako Ono, Hideki Ohmomo, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Akira Takashima, So Umekage, Motoki Iwasaki, Atsushi Shimizu

    Thyroid : official journal of the American Thyroid Association　32　(2)　188-195　2022/02

    DOI： 10.1089/thy.2021.0417 　

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    Background: Expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) plays a major role as a "danger signal" on stressed cells to promote removal of the latter by NKG2D-expressing cytotoxic lymphocytes. NKG2DL expression has been found in peripheral immune cells as well, such as in macrophages; however, the effect of this expression is yet to be determined. Methods: We determined instrumental variables (IVs; R2 <0.01 in linkage disequilibrium), explaining the major variance in major histocompatibility complex class I chain-related protein A (MICA) and B (MICB) gene expression levels from the expression-quantitative trait locus (eQTL) of NKG2DLs based on the RNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from 381 Japanese. Simultaneously, the target outcomes were filtered by PheWAS from 58 health risks, using a community-based cohort study composed of 44,739 Japanese residents. Finally, we estimated the causal effect of gene expression levels on the outcomes using the Mendelian randomization approach. Results: We determined nine and four IVs, explaining 87.6% and 33.0% of MICA and MICB gene expression levels, respectively. In the association test, we identified 10 or 13 significant outcomes associated with the MICA or MICB eQTLs, respectively, as well as the causal effect of MICA expression on Graves' disease (GD) (p = 4.2 × 10-3; odds ratio per 1 S.D. difference in the expression: 0.983 [confidence interval: 0.971-0.995]), using the weighted median estimator, without significant pleiotropy (p > 0.05), and the results were consistent across the sensitivity analyses. Conclusions: Our study provide novel evidence associating NKG2DL expression with GD, an autoimmune thyroiditis; direction of the effect indicated the immunoregulatory role of MICA expression in PBMCs, suggesting the importance of further functional assays in inflammatory diseases.

  65. Stroke genetics informs drug discovery and risk prediction across ancestries

    Stéphanie Debette, Aniket Mishra, Rainer Malik, Tsuyoshi Hachiya, Tuuli Jürgenson, Shinichi Namba, Masaru Koido, Quentin Le Grand, Frederick Kamanu, Mingyang Shi, Yunye He, Marios Georgakis, Ilana Caro, Kristi Krebs, Felix Vaura, Naomi Habib, Bendik Winsvold, Yon Ho Jee, Jesper Qvist Thomassen, Vida Abedi, Jara Cárcel-Márquez, Kuang Lin, Marianne Nygaard, Ganesh Chauhan, Hampton Leonard, Chaojie Yang, Ekaterina Yonova-Doing, Maria Knol, Tetsuro Ago, Philippe Amouyel, Christopher Anderson, Nicole Armstrong, Mark Bakker, Traci Bartz, Joshua Bis, Constance Bordes, Sigrid Borte, Anael Cain, Paul Ridker, Zhengming Chen, Michael Chong, John Cole, Rafael de Cid, Matthias Endres, Leslie Ferreira, Natalie Gasca, Vilmundur Gudnason, Jun Hata, Aki Havulinna, Jemma Hopewell, Hyacinth Hyacinth, Michael Inouye, Mina Jacob, Christina  Jeon, Christina Jern, Masahiro Kamouchi, Keith Keene, Takanari Kitazono, Steven Kittner, Takahiro Konuma, Amit Kumar, Paul Lacaze, Lenore Launer, Kaido Lepik, Jiang Li, Liming Li, Ani Manichaikul, Hugh Markus, Nicholas Marston, Thomas Meitinger, Braxton Mitchell, Felipe Montellano, Takayuki Morisaki, Thomas Mosley, Mike Nalls, Børge Nordestgaard, Martin O'Donnell, Yukinori Okada, Guillaume Pare, Annette Peters, Bruce Psaty, Stephen Rich, Jonathan Rosand, Marc Sabatine, Ralph Sacco, Danish Saleheen, Else Charlotte Sandset, Muralidharan Sargurupremraj, Makoto Sasaki, Claudia Satizabal, Carsten Schmidt, Atsushi Shimizu, Nicholas Smith, Daniel Strbian, Yoichi Sutoh, Kozo Tanno, Steffen Tiedt, Nuria Torres-Aguila, David-Alexandre Trégouët, Stella Trompet, Anil Tuladhar, Anne Tybjærg-Hansen, Marion van Vugt, Riina Vibo, Kerri Wiggins, Daniel Woo, Huichun Xu, Qiong Yang, Mark Lathrop, Iona Millwood, Christian Gieger, Toshiharu Ninomiya, Hans Grabe, J Wouter Jukema, Ina Rissanen, Sudha Seshadri, William Longstreth, Daniel Chasman, Joanna Howson, Marguerite Irvin, Hieab Adams, Sylvia Wasssertheil-Smoller, Kaare Christensen, M. Arfan Ikram, Tatjana Rundek, Jerome Rotter, Moeen Riaz, Eleanor Simonsick, Janika Kõrv, Paulo França, Myriam Fornage, Ramin Zand, Kameshwar Prasad, Ruth Frikke-Schmidt, Frank-Erik de Leeuw, Thomas Liman, Karl Georg Haeusler, Ynte Ruigrok, Peter Heuschmann, Keum Jung, John-Anker Zwart, Teemu Niiranen, Christian Ruff, Israel Fernández-Cadenas, Robin Walters, Lili Milani, Yoichiro Kamatani, Martin Dichgans

    2022/01/04

    Publisher: Research Square Platform LLC

    DOI： 10.21203/rs.3.rs-1175817/v1 　

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    Abstract Previous genome-wide association studies (GWAS) of stroke, the second leading cause of death, have been conducted in populations of predominantly European ancestry.1,2 We undertook cross-ancestry GWAS meta-analyses of stroke and its subtypes in 110,182 stroke patients (33% non-European) and 1,503,898 control individuals of five ancestries from population- and clinic-based studies, nearly doubling the number of cases in previous stroke GWAS. We identified association signals at 89 independent loci, of which 61 were novel. Effect sizes were overall highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis using a novel machine-learning approach,3 transcriptome and proteome-wide association analyses revealed putative causal genes (e.g. SH3PXD2A and FURIN) and variants (e.g. at GRK5 and NOS3). Using a novel three-pronged approach,4 we provided genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWAS with vascular risk factor GWAS (iPGS) showed strong prediction of ischemic stroke risk in European and, for the first time, East-Asian populations.5,6 The iPGS performed better than stroke PGS alone and better than previous best iPGS, in Europeans and East-Asians. Transferability of European-specific iPGS to East-Asians was limited. Stroke genetic risk scores were predictive of ischemic stroke independent of clinical risk factors in 52,600 clinical trial participants with cardiometabolic disease and performed considerably better than previous scores, both in Europeans and East-Asians. Altogether our results provide critical insight to inform biology, reveal potential drug targets for intervention, and provide genetic risk prediction tools across ancestries for targeted prevention.

  66. メンデルのランダム化法による血中脂質と大腸がんの関係の検討

    岩上 将夫, 後藤 温, 鈴木 詩織, 片桐 諒子, 羽入田 明子, 山地 太樹, 澤田 典絵, 中杤 昌弘, 若井 建志, 須藤 洋一, 清水 厚志, 丹野 高三, 木下 賢吾, 寳澤 篤, 伊藤 秀美, 松尾 恵太郎, 岩崎 基, J-CGEグループ

    Journal of Epidemiology　32　(Suppl.1)　155-155　2022/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  67. メンデルのランダム化法による糖代謝指標と大腸がんの関連解析

    羽入田 明子, 後藤 温, 鈴木 詩織, 片桐 諒子, 岩上 将夫, 山地 太樹, 澤田 典絵, 中杤 昌弘, 若井 建志, 須藤 洋一, 清水 厚志, 丹野 高三, 木下 賢吾, 寳澤 篤, 伊藤 秀美, 松尾 恵太郎, 岩崎 基

    Journal of Epidemiology　32　(Suppl.1)　155-155　2022/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  68. A genome-wide association study on confection consumption in a Japanese population: the Japan Multi-Institutional Collaborative Cohort Study. International-journal

    Taro Suzuki, Yasuyuki Nakamura, Yukio Doi, Akira Narita, Atsushi Shimizu, Nahomi Imaeda, Chiho Goto, Kenji Matsui, Aya Kadota, Katsuyuki Miura, Masahiro Nakatochi, Keitaro Tanaka, Megumi Hara, Hiroaki Ikezaki, Masayuki Murata, Toshiro Takezaki, Daisaku Nishimoto, Keitaro Matsuo, Isao Oze, Nagato Kuriyama, Etsuko Ozaki, Haruo Mikami, Yohko Nakamura, Miki Watanabe, Sadao Suzuki, Sakurako Katsuura-Kamano, Kokichi Arisawa, Kiyonori Kuriki, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Yoshikuni Kita, Kenji Wakai

    The British journal of nutrition　126　(12)　1843-1851　2021/12/28

    DOI： 10.1017/S0007114521000684 　

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    Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1-3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

  69. 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.

  70. Association between the social isolation and depressive symptoms after the great East Japan earthquake: findings from the baseline survey of the TMM CommCohort study

    Yuka Kotozaki, Kozo Tanno, Kiyomi Sakata, Eri Takusari, Kotaro Otsuka, Hiroaki Tomita, Ryohei Sasaki, Nobuyuki Takanashi, Takahiro Mikami, Atsushi Hozawa, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Akira Narita, Yasuyuki Taki, Atsushi Shimizu, Jiro Hitomi, Mamoru Satoh, Makoto Sasaki

    BMC Public Health　21　(1)　2021/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1186/s12889-021-10896-5 　

    eISSN： 1471-2458

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    <title>Abstract</title><sec> <title>Background</title> Social isolation and mental health issues have become a severe problem in disaster areas in the Great East Japan Earthquake. This study examined whether the combination of the house damage and social isolation or the combination of the death of family members and social isolation is associated with depressive symptoms among survivors using the baseline study data of the Tohoku Medical Megabank Project Community-Based Cohort Study (TMM CommCohort Study). </sec><sec> <title>Methods</title> We used cross-sectional data from a baseline survey of 48,958 participants (18,423 males, 30,535 females; aged 60.1 ± 11.2 years) to examine the association between social isolation measured by the Lubben social network scale 6 (LSNS-6) and depressive symptoms measured by the Center for Epidemiological Studies-Depressive Scale (CES-D). The presence of social isolation and depressive symptoms was defined by an LSNS-6 score of &lt; 12 and a CES-D score of ≥16, respectively. We performed a logistic regression analysis to determine the multivariable-adjusted odds ratio (95% confidence interval) [AOR (95% CI)] for depressive symptoms according to sex in the social isolation in comparison to without social isolation, and the associations of the combination of the house damage or the death of family members and social isolation and depressive symptoms. </sec><sec> <title>Results</title> Social isolation was significantly associated with depressive symptoms (males: OR = 1.87; 95% CI = 1.72–2.04, females: OR = 2.13; 95% CI = 2.00–2.26). Both males and females respondents with severe house damage and social isolation had a greater risk of depressive symptoms in comparison to those with an undamaged house and without social isolation (males: OR = 3.40; 95% CI = 2.73–4.24, females: OR = 2.92; 95% CI = 2.46–3.46). The risk of depressive symptoms was also higher in both males and females respondents with the death of family members and social isolation in comparison to those without the death of family members and without social isolation (males: OR = 2.18; 95% CI = 1.90–2.50, females: OR = 2.60; 95% CI = 2.35–2.88). </sec><sec> <title>Conclusion</title> The findings suggested that a combination of social isolation and severe house damage and the death of family members caused by a large-scale natural disaster was associated with a higher risk of depressive symptoms although the interaction was not statistically significant. </sec>

  71. 出生コホート連携に基づく胎児期から乳幼児期の環境と母児の予後との関連に関する研究

    小原 拓, 岸 玲子, 佐田 文宏, 清水 厚志, 菅原 準一, 土屋 賢治, 堀川 玲子, 目時 弘仁, 森崎 菜穂, 森 千里, 栗山 進一

    DOHaD研究　9　(1)　77-77　2021/09

    Publisher: (一社)日本DOHaD学会

    ISSN： 2187-2562

    eISSN： 2187-2597

  72. A genome-wide association study in Japanese identified one variant associated with a preference for a Japanese dietary pattern. International-journal

    Harumitsu Suzuki, Yasuyuki Nakamura, Keitaro Matsuo, Nahomi Imaeda, Chiho Goto, Akira Narita, Atsushi Shimizu, Naoyuki Takashima, Kenji Matsui, Katsuyuki Miura, Masahiro Nakatochi, Asahi Hishida, Takashi Tamura, Yuka Kadomatsu, Rieko Okada, Yuichiro Nishida, Chisato Shimanoe, Daisaku Nishimoto, Toshiro Takezaki, Isao Oze, Hidemi Ito, Hiroaki Ikezaki, Masayuki Murata, Daisuke Matsui, Etsuko Ozaki, Haruo Mikami, Yohko Nakamura, Sadao Suzuki, Miki Watanabe, Kokichi Arisawa, Hirokazu Uemura, Kiyonori Kuriki, Yukihide Momozawa, Michiaki Kubo, Yoshikuni Kita, Kenji Takeuchi, Kenji Wakai

    European journal of clinical nutrition　75　(6)　937-945　2021/06

    DOI： 10.1038/s41430-020-00823-z 　

    ISSN： 0954-3007

    eISSN： 1476-5640

  73. Diversification of mineralocorticoid receptor genes in a subterranean rodent, the naked mole-rat. International-journal

    Kaori Oka, Hidemasa Bono, Asato Kuroiwa, Shusuke Fujioka, Atsushi Shimizu, Yoshinao Katsu, Kyoko Miura

    Journal of molecular endocrinology　66　(4)　299-311　2021/05/11

    DOI： 10.1530/JME-20-0325 　

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    Naked mole-rats (Heterocephalus glaber) inhabit subterranean burrows in savannas and are, thus, unable to access free water. To identify their mechanism of osmoregulation in xeric environments, we molecularly cloned and analyzed the nuclear receptor subfamily 3 group C member 2 (NR3C2) gene encoding the mineralocorticoid receptor (MR), required for hormone-dependent regulation of genes contributing to body fluid homeostasis. Most vertebrates harbor a single MR homolog. In contrast, we discovered that MR is duplicated in naked mole-rats. The amino acid sequence of naked mole-rat MR1 is 90% identical to its mouse ortholog, and MR1 is abundantly expressed in the kidney and the nervous system. MR2 encodes a truncated protein lacking DNA- and ligand-binding domains of MR1 and is expressed in diverse tissues. Although MR2 did not directly transactivate gene expression, it increased corticosteroid-dependent transcriptional activity of MR1. Our results suggest that MR2 might function as a novel regulator of MR1 activity to fine-tune MR signaling in naked mole-rats.

  74. A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK-ZNF890P locus in the Japanese general population. International-journal

    Takahito Nasu, Mamoru Satoh, Tsuyoshi Hachiya, Yoichi Sutoh, Hideki Ohmomo, Sho Hitomi, Satoru Taguchi, Hiroto Kikuchi, Takamasa Kobayashi, Yuji Takahashi, Takuya Osaki, Yoshihiro Morino, Kenji Sobue, Atsushi Shimizu, Makoto Sasaki

    International journal of cardiology　329　186-191　2021/04/15

    DOI： 10.1016/j.ijcard.2020.12.019 　

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    BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor for CVD in the Japanese general population. METHODS: This was a genome-wide association study (GWAS) based on a cohort from the 2013 Tohoku Medical Megabank Project community study. The GWAS was performed using a HumanOmniExpressExome BeadChip array with 914,035 autosomal single-nucleotide polymorphisms. The Framingham Risk Score and the Suita score were used to evaluate the future risk of CVD. RESULTS: The GWAS identified 10 loci reaching suggestive significance in the discovery cohort. A replication analysis confirmed that one of the 10 loci, rs7798496, is associated with elevated hs-cTnT levels. The combined P value in the discovery and replication cohorts for the association between the rs7798496 and hs-cTnT levels was 3.4 × 10-8, which indicates that the novel variant reached genome-wide significance. The rs7798496 loci was located at an intergenic region between the retinoblastoma gene product (RB)-associated Krüppell-associated box (KRAB) zinc finger, zinc finger protein 890, and pseudogene (ZNF890P). Logistic regression analysis revealed that the presence of the rs7798496 T allele was strongly associated with a high risk for CVD. CONCLUSIONS: This study provides insights into a link between a novel genetic variant, T allele of rs7798269, and elevated hs-cTnT levels as a future risk for CVD in the general Japanese population.

  75. Body mass index and colorectal cancer risk: A Mendelian randomization study. International-journal

    Shiori Suzuki, Atsushi Goto, Masahiro Nakatochi, Akira Narita, Taiki Yamaji, Norie Sawada, Ryoko Katagiri, Masao Iwagami, Akiko Hanyuda, Tsuyoshi Hachiya, Yoichi Sutoh, Isao Oze, Yuriko N Koyanagi, Yumiko Kasugai, Yukari Taniyama, Hidemi Ito, Hiroaki Ikezaki, Yuichiro Nishida, Takashi Tamura, Haruo Mikami, Toshiro Takezaki, Sadao Suzuki, Etsuko Ozaki, Kiyonori Kuriki, Naoyuki Takashima, Kokichi Arisawa, Kenji Takeuchi, Kozo Tanno, Atsushi Shimizu, Gen Tamiya, Atsushi Hozawa, Kengo Kinoshita, Kenji Wakai, Makoto Sasaki, Masayuki Yamamoto, Keitaro Matsuo, Shoichiro Tsugane, Motoki Iwasaki

    Cancer science　112　(4)　1579-1588　2021/04

    DOI： 10.1111/cas.14824 　

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    Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2 ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.

  76. A genome-wide association study on fish consumption in a Japanese population-the Japan Multi-Institutional Collaborative Cohort study. International-journal

    Taro Suzuki, Yasuyuki Nakamura, Keitaro Matsuo, Isao Oze, Yukio Doi, Akira Narita, Atsushi Shimizu, Nahomi Imaeda, Chiho Goto, Kenji Matsui, Masahiro Nakatochi, Katsuyuki Miura, Naoyuki Takashima, Kiyonori Kuriki, Chisato Shimanoe, Keitaro Tanaka, Hiroaki Ikezaki, Masayuki Murata, Rie Ibusuki, Toshiro Takezaki, Yuriko Koyanagi, Hidemi Ito, Daisuke Matsui, Teruhide Koyama, Haruo Mikami, Yohko Nakamura, Sadao Suzuki, Takeshi Nishiyama, Sakurako Katsuura-Kamano, Kokichi Arisawa, Kenji Takeuchi, Takashi Tamura, Rieko Okada, Yoko Kubo, Yukihide Momozawa, Michiaki Kubo, Yoshikuni Kita, Kenji Wakai

    European journal of clinical nutrition　75　(3)　480-488　2021/03

    DOI： 10.1038/s41430-020-00702-7 　

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    BACKGROUND/OBJECTIVE: Although benefits of fish consumption for health are well known, a significant percentage of individuals dislike eating fish. Fish consumption may be influenced by genetic factors in addition to environmental factors. We conducted a genome-wide association study (GWAS) to find genetic variations that affect fish consumption in a Japanese population. METHODS: We performed a two-stage GWAS on fish consumption using 13,739 discovery samples from the Japan Multi-Institutional Collaborative Cohort study, and 2845 replication samples from the other population. We used a semi-quantitative food frequency questionnaire to estimate food intake. Association of the imputed variants with fish consumption was analyzed by separate linear regression models per variant, with adjustments for age, sex, energy intake, principal component analysis components 1-10, and alcohol intake (g/day). We also performed conditional analysis. RESULTS: We found 27 single nucleotide polymorphisms (SNPs) located in 12q24 and 14q32.12 that were associated with fish consumption. The 19 SNPs were located at 11 genes including six lead SNPs at the BRAP, ACAD10, ALDH2, NAA25, and HECTD4 regions on 12q24.12-13, and CCDC197 region on 14q32.12. In replication samples, all five SNPs located on chromosome 12 were replicated successfully, but the one on chromosome 14 was not. Conditional analyses revealed that the five lead variants in chromosome 12 were in fact the same signal. CONCLUSION: We found that new SNPs in the 12q24 locus were related to fish intake in two Japanese populations. The associations between SNPs on chromosome 12 and fish intake were strongly confounded by drinking status.

  77. Plasma Xanthine Oxidoreductase Activity Is Associated with a High Risk of Cardiovascular Disease in a General Japanese Population. International-journal

    Yuka Kotozaki, Mamoru Satoh, Kozo Tanno, Hideki Ohmomo, Ryo Otomo, Fumitaka Tanaka, Takahito Nasu, Satoru Taguchi, Hiroto Kikuchi, Takamasa Kobayashi, Atsushi Shimizu, Kiyomi Sakata, Jiro Hitomi, Kenji Sobue, Makoto Sasaki

    International journal of environmental research and public health　18　(4)　1894-1894　2021/02/16

    Publisher: MDPI AG

    DOI： 10.3390/ijerph18041894 　

    eISSN： 1660-4601

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    The purpose of this study was to investigate the association between xanthine oxidoreductase (XOR) activity and a high risk of cardiovascular disease (CVD) in a general Japanese population. The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture. The cardiovascular risk was calculated using the Framingham risk score (FRS). A total of 1605 of the 1631 participants (98.4%) had detectable XOR activity. Multiple regression analysis demonstrated that XOR activity was independently associated with body mass index (β = 0.26, p &lt; 0.001), diabetes (β = 0.09, p &lt; 0.001), dyslipidemia (β = 0.08, p = 0.001), and uric acid (β = 0.13, p &lt; 0.001). Multivariate analysis showed that the highest quartile of XOR activity was associated with a high risk for CVD (FRS ≥15) after adjustment for baseline characteristics (OR 2.93, 95%CI 1.16–7.40). The area under the receiver operating characteristic curves of the FRS with XOR activity was 0.81 (p = 0.008). XOR activity is associated with a high risk for CVD, suggesting that high XOR activity may indicate cardiovascular risk in a general Japanese population.

  78. Identification of epigenetic memory candidates associated with gestational age at birth through analysis of methylome and transcriptional data. International-journal

    Kohei Kashima, Tomoko Kawai, Riki Nishimura, Yuh Shiwa, Kevin Y Urayama, Hiromi Kamura, Kazue Takeda, Saki Aoto, Atsushi Ito, Keiko Matsubara, Takeshi Nagamatsu, Tomoyuki Fujii, Isaku Omori, Mitsumasa Shimizu, Hironobu Hyodo, Koji Kugu, Kenji Matsumoto, Atsushi Shimizu, Akira Oka, Masashi Mizuguchi, Kazuhiko Nakabayashi, Kenichiro Hata, Naoto Takahashi

    Scientific reports　11　(1)　3381-3381　2021/02/09

    DOI： 10.1038/s41598-021-83016-3 　

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    Preterm birth is known to be associated with chronic disease risk in adulthood whereby epigenetic memory may play a mechanistic role in disease susceptibility. Gestational age (GA) is the most important prognostic factor for preterm infants, and numerous DNA methylation alterations associated with GA have been revealed by epigenome-wide association studies. However, in human preterm infants, whether the methylation changes relate to transcription in the fetal state and persist after birth remains to be elucidated. Here, we identified 461 transcripts associated with GA (range 23-41 weeks) and 2093 candidate CpG sites for GA-involved epigenetic memory through analysis of methylome (110 cord blood and 47 postnatal blood) and transcriptional data (55 cord blood). Moreover, we discovered the trends of chromatin state, such as polycomb-binding, among these candidate sites. Fifty-four memory candidate sites showed correlation between methylation and transcription, and the representative corresponding gene was UCN, which encodes urocortin.

  79. Evaluation of clinical formalin-fixed paraffin-embedded tissue quality for targeted-bisulfite sequencing. International-journal

    Hideki Ohmomo, Shohei Komaki, Kanako Ono, Yoichi Sutoh, Tsuyoshi Hachiya, Eri Arai, Hiroyuki Fujimoto, Teruhiko Yoshida, Yae Kanai, Makoto Sasaki, Atsushi Shimizu

    Pathology international　71　(2)　135-140　2021/02

    DOI： 10.1111/pin.13054 　

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    Formalin-fixed paraffin-embedded (FFPE) tissues are promising biological resources for genetic research. Recent improvements in DNA extraction from FFPE samples allowed the use of these tissues for multiple sequencing methods. However, fundamental research addressing the application of FFPE-derived DNA for targeted-bisulfite sequencing (TB-seq) is lacking. Here, we evaluated the suitability of FFPE-derived DNA for TB-seq. We conducted TB-seq using FFPE-derived DNA and corresponding fresh frozen (FF) tissues of patients with kidney cancer and compared the quality of DNA, libraries, and TB-seq statistics between the two preservation methods. The approximately 600-bp average fragment size of the FFPE-derived DNA was significantly shorter than that of the FF-derived DNA. The sequencing libraries constructed using FFPE-derived DNA and the mapping ratio were approximately 10 times and 10% lower, respectively, than those constructed using FF-derived DNA. In the mapped data of FFPE-derived DNA, duplicated reads accounted for > 60% of the obtained sequence reads, with lower mean on-target coverage. Therefore, the standard TB-seq protocol is inadequate for obtaining high-quality data for epigenetic analysis from FFPE-derived DNA, and technical improvements are necessary for enabling the use of archived FFPE resources.

  80. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. International-journal

    Hirofumi Zempo, Su-Jeong Kim, Noriyuki Fuku, Yuichiro Nishida, Yasuki Higaki, Junxiang Wan, Kelvin Yen, Brendan Miller, Roberto Vicinanza, Eri Miyamoto-Mikami, Hiroshi Kumagai, Hisashi Naito, Jialin Xiao, Hemal H Mehta, Changhan Lee, Megumi Hara, Yesha M Patel, Veronica W Setiawan, Timothy M Moore, Andrea L Hevener, Yoichi Sutoh, Atsushi Shimizu, Kaname Kojima, Kengo Kinoshita, Yasumichi Arai, Nobuyoshi Hirose, Seiji Maeda, Keitaro Tanaka, Pinchas Cohen

    Aging　13　(2)　1692-1717　2021/01/19

    Publisher: Impact Journals, LLC

    DOI： 10.18632/aging.202529 　

    eISSN： 1945-4589

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    Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

  81. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. International-journal

    Shu Tadaka, Eiji Hishinuma, Shohei Komaki, Ikuko N Motoike, Junko Kawashima, Daisuke Saigusa, Jin Inoue, Jun Takayama, Yasunobu Okamura, Yuichi Aoki, Matsuyuki Shirota, Akihito Otsuki, Fumiki Katsuoka, Atsushi Shimizu, Gen Tamiya, Seizo Koshiba, Makoto Sasaki, Masayuki Yamamoto, Kengo Kinoshita

    Nucleic acids research　49　(D1)　D536-D544　2021/01/08

    DOI： 10.1093/nar/gkaa1034 　

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    In the Tohoku Medical Megabank project, genome and omics analyses of participants in two cohort studies were performed. A part of the data is available at the Japanese Multi Omics Reference Panel (jMorp; https://jmorp.megabank.tohoku.ac.jp) as a web-based database, as reported in our previous manuscript published in Nucleic Acid Research in 2018. At that time, jMorp mainly consisted of metabolome data; however, now genome, methylome, and transcriptome data have been integrated in addition to the enhancement of the number of samples for the metabolome data. For genomic data, jMorp provides a Japanese reference sequence obtained using de novo assembly of sequences from three Japanese individuals and allele frequencies obtained using whole-genome sequencing of 8,380 Japanese individuals. In addition, the omics data include methylome and transcriptome data from ∼300 samples and distribution of concentrations of more than 755 metabolites obtained using high-throughput nuclear magnetic resonance and high-sensitivity mass spectrometry. In summary, jMorp now provides four different kinds of omics data (genome, methylome, transcriptome, and metabolome), with a user-friendly web interface. This will be a useful scientific data resource on the general population for the discovery of disease biomarkers and personalized disease prevention and early diagnosis.

  82. 客観的に測定された身体活動と末梢血DNAメチル化の関連

    西田 裕一郎, 原 めぐみ, 大桃 秀樹, 小野 加奈子, 清水 厚志, 檜垣 靖樹, 田口 尚人, 島ノ江 千里, 堀田 美加子, 田中 恵太郎

    Journal of Epidemiology　31　(Suppl.)　127-127　2021/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  83. 客観的に測定された身体活動と末梢血DNAメチル化の関連

    西田裕一郎, 原めぐみ, 大桃秀樹, 小野加奈子, 清水厚志, 檜垣靖樹, 田口尚人, 島ノ江千里, 堀田美加子, 田中恵太郎

    日本疫学会学術総会講演集(Web)　31st　(Suppl.)　127-127　2021/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  84. Weight Gain After 20 Years of Age is Associated with Unfavorable Lifestyle and Increased Prevalence of Metabolic Disorders. International-journal

    Noriko Takebe, Kozo Tanno, Hideki Ohmomo, Mari Hangai, Tomoyasu Oda, Yutaka Hasegawa, Nobuyuki Takanashi, Ryohei Sasaki, Atsushi Shimizu, Akira Sasaki, Kiyomi Sakata, Makoto Sasaki, Yasushi Ishigaki

    Diabetes, metabolic syndrome and obesity : targets and therapy　14　2065-2075　2021

    DOI： 10.2147/DMSO.S300250 　

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    Purpose: It is unclear what kind of modifiable lifestyle factors are associated with long-time weight gain in adulthood. To clarify the lifestyle behavior related to body weight gain since the age of 20 years, we explored the lifestyle risk factor, independently associated with excessive weight gain after 20 years of age as compared to those in subjects with a stable weight, with matching of age, gender, and the current body mass index (BMI). Patients and Methods: From baseline data of a general population-based cohort study, we designed a cross-sectional analysis collecting individual data of medical health check-ups and a questionnaire related to lifestyle, including amount of sleep, frequency of eating breakfast, average times per day engaged in walking and sitting in the prior year, and smoking habits. These data were compared between the subjects with weight gain ≥10kg (n=3601) and <10kg (n=3601) after age 20, matched by a propensity score model which included current BMI, age and gender. We used multivariable logistic regressions to assess the lifestyle factor's association with high weight gain. Results: Participants who gained ≥10 kg were significantly more likely to sleep <5 hours or ≥9 hours per night, skip breakfast, engage in walking <1 hour per day, and sit ≥5 hours per day than those who gained <10kg. Multivariable logistic regressions analyses showed that, with adjusting for potential confounder, the lifestyles with the positive association with high weight gain were skipping breakfast (OR 1.252; 95% CI 1.053-1.489, vs regularly), long sleeping duration (9 hours/day≤ OR 1.613; 95% CI 1.018-2.557 vs 5≤-<7 hours/day), and former smoker (OR 1.163; 95% CI 1.008-1.343 vs never smoker), while walking duration was negatively associated with high weight gain. Furthermore, despite similar current BMI, participants with weight gain ≥10kg had significantly higher values for waist circumference, blood pressure, HbA1c, LDL-C, triglycerides, and hepatic enzyme levels than those with weight gain <10kg. Similarly, the prevalence rates of hypertension, dyslipidemia, metabolic syndrome (MetS), and former smoker were higher in the participants with weight gain ≥10kg. Conclusion: Major weight gain after 20 years of age was associated with unfavorable lifestyle factors and greater waist circumference, possibly leading to elevated risk for MetS and other non-communicable diseases. These findings highlight the importance of maintaining both weight at age 20 and a favorable lifestyle throughout adulthood.

  85. Identification of a novel uterine leiomyoma GWAS locus in a Japanese population

    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)　2020/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-020-58066-8 　

    eISSN： 2045-2322

  86. 心血管・動脈硬化 地域住民コホートにおける脈波伝播速度(PWV)と生活習慣の関係

    武部 典子, 丹野 高三, 大桃 秀樹, 半谷 真理, 長谷川 豊, 清水 厚志, 坂田 清美, 佐々木 真理, 石垣 泰

    糖尿病合併症　34　(Suppl.1)　182-182　2020/11

    Publisher: (一社)日本糖尿病合併症学会

  87. 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.

  88. ALDH2 genotype modulates the association between alcohol consumption and AST/ALT ratio among middle-aged Japanese men: a genome-wide G × E interaction analysis. International-journal

    Yoichi Sutoh, Tsuyoshi Hachiya, Yuji Suzuki, Shohei Komaki, Hideki Ohmomo, Keisuke Kakisaka, Ting Wang, Yasuhiro Takikawa, Atsushi Shimizu

    Scientific reports　10　(1)　16227-16227　2020/10/01

    DOI： 10.1038/s41598-020-73263-1 　

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    Liver tests (LT), especially to measure AST, ALT and GGT levels, are widely used to evaluate the risk of alcohol-related liver disease (ALD). In this study, we investigated the potential genetic factors that modulate the association between LTs and alcohol consumption. We conducted a genome-wide interaction meta-analysis in 7856 Japanese subjects from Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) study recruited in 2013, and identified 2 loci (12q24 and 2p16) with genome-wide significance (P > 5 × 10-8). The significant variants in the 12q24 included rs671, a variant associated with alcohol intolerance and located at a coding exon of ALDH2. We found that the amount of alcohol consumption was associated with increased level AST/ALT ratio among the subjects with the rs671 GA genotype. The elevated AST/ALT ratio among subjects with moderate-to-high levels of drinking behavior and the rs671 GA genotype was due to decreased levels of ALT, which was not accompanied with significant differences in AST levels. Although the interaction effect was significant in both men and women, the effect was much larger in men. Our results suggest that the impact of alcohol consumption on LT varies according to the ALDH2 genotype, providing an insight for the accurate screening of ALD in drinkers with the rs671 GA genotype.

  89. Machine learning for effectively avoiding overfitting is a crucial strategy for the genetic prediction of polygenic psychiatric phenotypes. International-journal

    Yuta Takahashi, Masao Ueki, Gen Tamiya, Soichi Ogishima, Kengo Kinoshita, Atsushi Hozawa, Naoko Minegishi, Fuji Nagami, Kentaro Fukumoto, Kotaro Otsuka, Kozo Tanno, Kiyomi Sakata, Atsushi Shimizu, Makoto Sasaki, Kenji Sobue, Shigeo Kure, Masayuki Yamamoto, Hiroaki Tomita

    Translational psychiatry　10　(1)　294-294　2020/08/17

    DOI： 10.1038/s41398-020-00957-5 　

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    The accuracy of previous genetic studies in predicting polygenic psychiatric phenotypes has been limited mainly due to the limited power in distinguishing truly susceptible variants from null variants and the resulting overfitting. A novel prediction algorithm, Smooth-Threshold Multivariate Genetic Prediction (STMGP), was applied to improve the genome-based prediction of psychiatric phenotypes by decreasing overfitting through selecting variants and building a penalized regression model. Prediction models were trained using a cohort of 3685 subjects in Miyagi prefecture and validated with an independently recruited cohort of 3048 subjects in Iwate prefecture in Japan. Genotyping was performed using HumanOmniExpressExome BeadChip Arrays. We used the target phenotype of depressive symptoms and simulated phenotypes with varying complexity and various effect-size distributions of risk alleles. The prediction accuracy and the degree of overfitting of STMGP were compared with those of state-of-the-art models (polygenic risk scores, genomic best linear-unbiased prediction, summary-data-based best linear-unbiased prediction, BayesR, and ridge regression). In the prediction of depressive symptoms, compared with the other models, STMGP showed the highest prediction accuracy with the lowest degree of overfitting, although there was no significant difference in prediction accuracy. Simulation studies suggested that STMGP has a better prediction accuracy for moderately polygenic phenotypes. Our investigations suggest the potential usefulness of STMGP for predicting polygenic psychiatric conditions while avoiding overfitting.

  90. Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a poikilothermic mammal

    Yuki Oiwa, Kaori Oka, Hironobu Yasui, Kei Higashikawa, Hidemasa Bono, Yoshimi Kawamura, Shingo Miyawaki, Akiyuki Watarai, Takefumi Kikusui, Atsushi Shimizu, Hideyuki Okano, Yuji Kuge, Kazuhiro Kimura, Yuko Okamatsu-Ogura, Kyoko Miura

    2020/04/29

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2020.04.28.062737 　

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    <title>Abstract</title>The naked mole-rat (NMR) is a poikilothermic mammal that forms eusocial colonies consisting of one breeding queen, several breeding kings, and subordinates. Despite their poikilothermic feature, NMRs possess brown adipose tissue (BAT), which in homeothermic mammals induces thermogenesis in cold environments. However, NMR-BAT thermogenic potential is controversial, and its physiological roles are unknown. Here, we show that NMR-BAT has beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential, which contributes to thermogenesis in the isolated queen in non-cold environments. NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity <italic>in vitro</italic> and <italic>in vivo</italic>. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment, it was insufficient to maintain the body temperatures of the NMRs. In a non-cold environment, NMRs are known to increase their body temperature by a heat-sharing behavior. Interestingly, we found that the body temperatures of NMRs isolated from the colony were also significantly higher than the ambient temperature. We also show that queens, but not subordinates, induce BAT thermogenesis in isolated, non-cold conditions. Our research provides novel insights into the role and mechanism of thermoregulation in this unique poikilothermic mammal.

  91. Author Correction: Characterizing rare and low-frequency height-associated variants in the Japanese population. International-journal Peer-reviewed

    Masato Akiyama, Kazuyoshi Ishigaki, Saori Sakaue, Yukihide Momozawa, Momoko Horikoshi, Makoto Hirata, Koichi Matsuda, Shiro Ikegawa, Atsushi Takahashi, Masahiro Kanai, Sadao Suzuki, Daisuke Matsui, Mariko Naito, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Kozo Tanno, Makoto Sasaki, Atsushi Hozawa, Naoko Minegishi, Kenji Wakai, Shoichiro Tsugane, Atsushi Shimizu, Masayuki Yamamoto, Yukinori Okada, Yoshinori Murakami, Michiaki Kubo, Yoichiro Kamatani

    Nature communications　11　(1)　1350-1350　2020/03/09

    DOI： 10.1038/s41467-020-15202-2 　

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    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  92. Abstract P539: The Association Between Social Isolation and Metabolic Syndrome in Japanese Adults: The Tohoku Medical Megabank Project Peer-reviewed

    Yuka Kotozaki, Kozo Tanno, Kotaro Otsuka, Ryouhei Sasaki, Nobuyuki Takanashi, Takahiro Mikami, Tomohiro Nakamura, Atsushi Hozawa, Koichi Asahi, Mamoru Satoh, Atsushi Shimizu, Yasushi Ishigaki, Kiyomi Sakata, Makoto Sasaki

    Circulation　141　(Suppl_1)　2020/03/03

    Publisher: Ovid Technologies (Wolters Kluwer Health)

    DOI： 10.1161/circ.141.suppl_1.p539 　

    ISSN： 0009-7322

    eISSN： 1524-4539

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    Metabolic syndrome (MetS) and its components are well established as risk factors for cardiovascular disease (CVD). On the other hand, it has also been reported that social isolation is associated with an increased risk of CVD. However, the relationship between social isolation and MetS and its components is not clear. Thus, the purpose of this study is to investigate the association between social isolation and the number of MetS components in Japanese adults. Participants were 28,917 individuals (male/female = 10,226/18,691, age = 59.9±11.6 years) from the Iwate area of the Tohoku Medical Megabank Organization Community-based cohort study (TMM CommCohort study). They had no history of coronary heart disease or stroke. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6). The participants were classified into two groups, the social isolation group and the non-isolation group, based on a cutoff point of 11/12 on the LSNS-6. An assessment of MetS used the criteria defined by the Japanese societies’ committee. The multivariate-adjusted odds ratios (95% confidence intervals) [AORs (95% CIs)] of the social isolation group versus the non-isolation group were calculated using ordered logistic analyses and compared to the number of MetS components. We used gender, age, education, current smoker, current alcohol drinker, total physical activity, current job status, and depression as covariates. AORs (95% CIs) of social isolation against non-isolation were 1.02 (0.95-1.09) for one component of MetS, 1.09 (1.01-1.19) for two components of MetS, and 1.16 (1.06-1.28) for three or more components of MetS, when compared to 0 component of MetS. In conclusion, Japanese adults who experience social isolation might have a greater number of MetS components.

  93. A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression Peer-reviewed

    C. Shimanoe, T. Hachiya, M. Hara, Y. Nishida, K. Tanaka, Y. Sutoh, A. Shimizu, A. Hishida, S. Kawai, R. Okada, T. Tamura, K. Matsuo, H. Ito, E. Ozaki, D. Matsui, R. Ibusuki, I. Shimoshikiryo, N. Takashima, A. Kadota, K. Arisawa, H. Uemura, S. Suzuki, M. Watanabe, K. Kuriki, K. Endoh, H. Mikami, Y. Nakamura, Y. Momozawa, M. Kubo, M. Nakatochi, M. Naito, K. Wakai

    Genes, Brain and Behavior　18　(2)　2020/02

    Publisher: WILEY

    DOI： 10.1111/gbb.12481 　

    ISSN： 1601-1848

    eISSN： 1601-183X

  94. 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

  95. Study profile of The Tohoku Medical Megabank Community-Based Cohort Study. Peer-reviewed

    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, Tomohiro 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　2020/01/11

    DOI： 10.2188/jea.JE20190271 　

    ISSN： 0917-5040

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    BackgroundWe established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environmental interactions on the incidence of major diseases such as cancer and cardiovascular diseases.MethodsWe asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria was 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), for example, carotid echography, calcaneal ultrasound bone mineral density, and so on. All participants agreed to measure genome information and to distribute their information widely.ResultsAs a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants with Type 1 survey were more likely to have psychological distress than those of 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.ConclusionThis cohort comprised large sample size and it contains information on 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 disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

  96. Epigenome-wide Association Study Identifies a Novel DNA Methylation in Patients with Severe Aortic Valve Stenosis. International-journal Peer-reviewed

    Nasu T, Satoh M, Ohmono H, Shiwa Y, Komaki S, Ono K, Shimizu A, Taguchi S, Takahashi Y, Osaki T, Morino Y, Sobue K, Sasaki M

    Circulation. Genomic and precision medicine　13　(1)　e002649　2020/01

    DOI： 10.1161/CIRCGEN.119.002649 　

  97. The interaction between ABCA1 polymorphism and physical activity on the HDL-cholesterol levels in a Japanese population. International-journal Peer-reviewed

    Nishida Y, Hachiya T, Hara M, Shimanoe C, Tanaka K, Sutoh Y, Shimizu A, Hishida A, Tsukamoto M, Kadomatsu Y, Oze I, Koyanagi YN, Kuriyama N, Koyama T, Ibusuki R, Takezaki T, Ikezaki H, Furusyo N, Takashima N, Kadota A, Uemura H, Katsuura-Kamano S, Suzuki S, Nakagawa-Senda H, Kuriki K, Mikami H, Nakamura Y, Momozawa Y, Kubo M, Nakatochi M, Naito M, Wakai K, Japan Multi-Institutional Collaborative Cohort, Study Group

    Journal of lipid research　61　(1)　86-94　2020/01

    DOI： 10.1194/jlr.P091546 　

    ISSN： 0022-2275

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    Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [P-interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (β = 0.008) compared with those with medium (β = 0.032) or high PA (β = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men.

  98. Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population. International-journal Peer-reviewed

    Low SK, Chin YM, Ito H, Matsuo K, Tanikawa C, Matsuda K, Saito H, Sakurai-Yageta M, Nakaya N, Shimizu A, Nishizuka SS, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Takezaki T, Suzuki S, Naito M, Wakai K, Kamatani Y, Momozawa Y, Murakami Y, Inazawa J, Nakamura Y, Kubo M, Katagiri T, Miki Y

    Scientific reports　9　(1)　17332-17332　2019/11

    DOI： 10.1038/s41598-019-53654-9 　

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    Genome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P < 5.0 × 10-8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 (ALCAM) and rs75286142 on 21q22.12 (CLIC6-RUNX1). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that individuals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to individuals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population.

  99. 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population. Peer-reviewed

    Takata R, Takahashi A, Fujita M, Momozawa Y, Saunders EJ, Yamada H, Maejima K, Nakano K, Nishida Y, Hishida A, Matsuo K, Wakai K, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Sasaki M, Shimizu A, Tanno K, Minegishi N, Suzuki K, Matsuda K, Kubo M, Inazawa J, Egawa S, Haiman CA, Ogawa O, Obara W, Kamatani Y, Akamatsu S, Nakagawa H

    Nature communications　10　(1)　4422　2019/09

    DOI： 10.1038/s41467-019-12267-6 　

    ISSN： 2041-1723

  100. Characterizing rare and low-frequency height-associated variants in the Japanese population. International-journal Peer-reviewed

    Akiyama M, Ishigaki K, Sakaue S, Momozawa Y, Horikoshi M, Hirata M, Matsuda K, Ikegawa S, Takahashi A, Kanai M, Suzuki S, Matsui D, Naito M, Yamaji T, Iwasaki M, Sawada N, Tanno K, Sasaki M, Hozawa A, Minegishi N, Wakai K, Tsugane S, Shimizu A, Yamamoto M, Okada Y, Murakami Y, Kubo M, Kamatani Y

    Nature communications　10　(1)　4393-4393　2019/09

    DOI： 10.1038/s41467-019-12276-5 　

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    Human height is a representative phenotype to elucidate genetic architecture. However, the majority of large studies have been performed in European population. To investigate the rare and low-frequency variants associated with height, we construct a reference panel (N = 3,541) for genotype imputation by integrating the whole-genome sequence data from 1,037 Japanese with that of the 1000 Genomes Project, and perform a genome-wide association study in 191,787 Japanese. We report 573 height-associated variants, including 22 rare and 42 low-frequency variants. These 64 variants explain 1.7% of the phenotypic variance. Furthermore, a gene-based analysis identifies two genes with multiple height-increasing rare and low-frequency nonsynonymous variants (SLC27A3 and CYP26B1; PSKAT-O < 2.5 × 10-6). Our analysis shows a general tendency of the effect sizes of rare variants towards increasing height, which is contrary to findings among Europeans, suggesting that height-associated rare variants are under different selection pressure in Japanese and European populations.

  101. Versican is crucial for the initiation of cardiovascular lumen development in medaka (Oryzias latipes). International-journal Peer-reviewed

    Nishant Mittal, Sung Han Yoon, Hirokazu Enomoto, Miyama Hiroshi, Atsushi Shimizu, Atsushi Kawakami, Misato Fujita, Hideto Watanabe, Keiichi Fukuda, Shinji Makino

    Scientific reports　9　(1)　9475-9475　2019/07/01

    DOI： 10.1038/s41598-019-45851-3 　

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    Versican is an evolutionary conserved extracellular matrix proteoglycan, and versican expression loss in mice results in embryonic lethality owing to cardiovascular defects. However, the in utero development of mammals limits our understanding of the precise role of versican during cardiovascular development. Therefore, the use of evolutionarily distant species that develop ex utero is more suitable for studying the mechanistic basis of versican activity. We performed ENU mutagenesis screening to identify medaka mutants with defects in embryonic cardiovascular development. In this study, we described a recessive point mutation in the versican 3'UTR resulting in reduced versican protein expression. The fully penetrant homozygous mutant showed termination of cardiac development at the linear heart tube stage and exhibited absence of cardiac looping, a constricted outflow tract, and no cardiac jelly. Additionally, progenitor cells did not migrate from the secondary source towards the arterial pole of the linear heart tube, resulting in a constricted outflow tract. Furthermore, mutants lacked blood flow and vascular lumen despite continuous peristaltic heartbeats. These results enhance our understanding of the mechanistic basis of versican in cardiac development, and this mutant represents a novel genetic model to investigate the mechanisms of vascular tubulogenesis.

  102. Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population. International-journal Peer-reviewed

    Takeshi Nishiyama, Masahiro Nakatochi, Atsushi Goto, Motoki Iwasaki, Tsuyoshi Hachiya, Yoichi Sutoh, Atsushi Shimizu, Chaochen Wang, Hideo Tanaka, Miki Watanabe, Akihiro Hosono, Yuya Tamai, Tamaki Yamada, Taiki Yamaji, Norie Sawada, Kentaro Fukumoto, Kotaro Otsuka, Kozo Tanno, Hiroaki Tomita, Kaname Kojima, Masao Nagasaki, Atsushi Hozawa, Asahi Hishida, Tae Sasakabe, Yuichiro Nishida, Megumi Hara, Hidemi Ito, Isao Oze, Yohko Nakamura, Haruo Mikami, Rie Ibusuki, Toshiro Takezaki, Teruhide Koyama, Nagato Kuriyama, Kaori Endoh, Kiyonori Kuriki, Tanvir C Turin, Takashima Naoyuki, Sakurako Katsuura-Kamano, Hirokazu Uemura, Rieko Okada, Sayo Kawai, Mariko Naito, Yukihide Momozawa, Michiaki Kubo, Makoto Sasaki, Masayuki Yamamoto, Shoichiro Tsugane, Kenji Wakai, Sadao Suzuki

    Sleep　42　(6)　2019/06/11

    DOI： 10.1093/sleep/zsz046 　

    ISSN： 0161-8105

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    Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

  103. Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population. International-journal Peer-reviewed

    Tanikawa C, Kamatani Y, Terao C, Usami M, Takahashi A, Momozawa Y, Suzuki K, Ogishima S, Shimizu A, Satoh M, Matsuo K, Mikami H, Naito M, Wakai K, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Kohri K, Yu ASL, Yasui T, Murakami Y, Kubo M, Matsuda K

    Journal of the American Society of Nephrology : JASN　30　(5)　855-864　2019/05

    DOI： 10.1681/ASN.2018090942 　

    ISSN： 1046-6673

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    BACKGROUND: A family history of urolithiasis is associated with a more than doubling of urolithiasis risk, and a twin study estimating 56% heritability of the condition suggests a pivotal role for host genetic factors. However, previous genome-wide association studies (GWAS) have identified only six risk-related loci. METHODS: To identify novel urolithiasis-related loci in the Japanese population, we performed a large-scale GWAS of 11,130 cases and 187,639 controls, followed by a replication analysis of 2289 cases and 3817 controls. Diagnosis of urolithiasis was confirmed either by a clinician or using medical records or self-report. We also assessed the association of urolithiasis loci with 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (such as body mass index, lipid storage, eGFR, serum uric acid, and serum calcium), using up to 160,000 samples from BioBank Japan. RESULTS: The analysis identified 14 significant loci, including nine novel loci. Ten regions showed a significant association with at least one quantitative trait, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic basis for urolithiasis and these quantitative traits. Four novel loci were related to metabolic traits, obesity, hypertriglyceridemia, or hyperuricemia. The remaining ten loci were associated with kidney- or electrolyte-related traits; these may affect crystallization. Weighted genetic risk score analysis indicated that the highest risk group (top 20%) showed an odds ratio of 1.71 (95% confidence interval, 1.42 to 2.06) - 2.13 (95% confidence interval, 2.00 to 2.27) compared with the reference group (bottom 20%). CONCLUSIONS: Our findings provide evidence that host genetic factors related to regulation of metabolic and crystallization pathways contribute to the development of urolithiasis.

  104. Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals International-journal Peer-reviewed

    Nishiyama T, Nakatochi M, Goto A, Iwasaki M, Hachiya T, Sutoh Y, Shimizu A, Wang C, Tanaka H, Watanabe M, Hosono A, Tamai Y, Yamada T, Yamaji T, Sawada N, Fukumoto K, Otsuka K, Tanno K, Tomita H, Kojima K, Nagasaki M, Hozawa A, Hishida A, Sasakabe T, Nishida Y, Hara M, Ito H, Oze I, Nakamura Y, Mikami H, Ibusuki R, Takezaki T, Koyama T, Kuriyama N, Endoh K, Kuriki K, Turin TC, Naoyuki T, Katsuura-Kamano S, Uemura H, Okada R, Kawai S, Naito M, Momozawa Y, Kubo M, Sasaki M, Yamamoto M, Tsugane S, Wakai K, Suzuki S

    Sleep　42　(6)　115-115　2019/02

    DOI： 10.1093/sleep/zsz046 　

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    Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (P<5 × 10-8) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci-TMEM18, TM4SF4, MXD3-LMAN2, PSORS1C1-PSORS1C2, and HNF4A-are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout.

  105. 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.

  106. GWAS identifies nine nephrolithiasis susceptibility loci related with metabolic metabolic and crystallization pathways

    Chizu Tanikawa, Yoichiro Kamatani, Chikashi Terao, Masayuki Usami, Atsushi Takahashi, Yukihide Momozawa, Kichiya Suzuki, Soichi Ogishima, Atsushi Shimizu, Mamoru Satoh, Keitaro Matsuo, Haruo Mikami, Mariko Naito, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Kenjiro Kohri, Takahiro Yasui, Yoshinori Murakami, Michiaki Kubo, Koichi Matsuda

    2019/01/13

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/519553 　

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    ABSTRACT Nephrolithiasis is a common urological trait disorder with acute pain. Although previous studies have identified various genetic variations associated with nephrolithiasis, the host genetic factors remain largely unidentified. To identify novel nephrolithiasis loci in the Japanese population, we performed large-scale GWAS (Genome wide association study) using 11,130 cases and 187,639 controls, followed by a replication analysis using 2,289 cases and 3,817 controls. The analysis identified 14 significant loci, including 9 novel loci on 2p23.2-3, 6p21.2, 6p12.3, 6q23.2, 16p12.3, 16q12.2, 17q23.2, 19p13.12, and 20q13.2. Interestingly, 10 of the 14 regions showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic background among nephrolithiasis patients and these quantitative traits. Four novel loci are related to the metabolic pathway, while the remaining 10 loci are associated with the crystallization pathway. Our findings demonstrate the crucial roles of genetic variations in the development of nephrolithiasis. SIGNIFICANCE STATEMENT Nephrolithiasis is a common urothelial disorders with frequent recurrence rate, but its genetic background is largely remained unidentified. Previous GWAS identified 6 genetic factors in total. Here we performed a GWAS using more than 200,000 samples in the Japanese populations, and identified 14 significant loci and nine of them are novel. We also found that 10 of the 14 loci showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (BMI, eGFR, UA, Ca etc). All 14 significant loci are associate with either metabolic or crystallization pathways. Thus, our findings elucidated the underlying molecular pathogenesis of nephrolithiasis.

  107. Plasma Xanthine Oxidoreductase Activity is Associated With Edothelial Dysfunction and Increased Arterial Stiffness in a General Japanese Population: the Iwate Tohoku Medical Megabank Project Peer-reviewed

    Yuka Kotozaki, Kozo Tanno, Hideki Ohmomo, Fumitaka Tanaka, Ryo Otomo, Atsushi Shimizu, Kiyomi Sakata, Jiro Hitomi, Makoto Sasaki, Mamoru Satoh

    CIRCULATION　139　2019

    DOI： 10.1161/circ.139.suppl_1.P031 　

    ISSN： 0009-7322

    eISSN： 1524-4539

  108. 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.

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

    Tanikawa, Chizu, Kamatani, Yoichiro, Toyoshima, Osamu, Sakamoto, Hiromi, Ito, Hidemi, Takahashi, Atsushi, Momozawa, Yukihide, Hirata, Makoto, Fuse, Nobuo, Takai-Igarashi, Takako, Shimizu, Atsushi, Sasaki, Makoto, Yamaji, Taiki, Sawada, Norie, Iwasaki, Mot

    CANCER SCIENCE　109　(12)　4015-4024　2018/12

    Publisher: WILEY

    DOI： 10.1111/cas.13815 　

    ISSN： 1349-7006

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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 ca

  110. 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.

  111. A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study Peer-reviewed

    Hiroko Nakagawa-Senda, Tsuyoshi Hachiya, Atsushi Shimizu, Satoyo Hosono, Isao Oze, Miki Watanabe, Keitaro Matsuo, Hidemi Ito, Megumi Hara, Yuichiro Nishida, Kaori Endoh, Kiyonori Kuriki, Sakurako Katsuura-Kamano, Kokichi Arisawa, Yora Nindita, Rie Ibusuki, Sadao Suzuki, Akihiro Hosono, Haruo Mikami, Yohko Nakamura, Naoyuki Takashima, Yasuyuki Nakamura, Nagato Kuriyama, Etsuko Ozaki, Norihiro Furusyo, Hiroaki Ikezaki, Masahiro Nakatochi, Tae Sasakabe, Sayo Kawai, Rieko Okada, Asahi Hishida, Mariko Naito, Kenji Wakai, Yukihide Momozawa, Michiaki Kubo, Hideo Tanaka

    Scientific Reports　8　(1)　1493　2018/12/01

    Publisher: Nature Publishing Group

    DOI： 10.1038/s41598-018-19914-w 　

    ISSN： 2045-2322

  112. マルチオミクスゲノムブラウザiMETHYLの紹介

    小巻 翔平, 志波 優, 古川 亮平, 八谷 剛史, 大桃 秀樹, 須藤 洋一, 大友 亮, 佐々木 真理, 清水 厚志

    トーゴーの日2018　1　2018/10/05

    Publisher: バイオサイエンスデータベースセンター

    DOI： 10.18908/togo2018.p048 　

  113. A comparison of genome cohort participants' genetic knowledge and preferences to receive genetic results before and after a genetics workshop. International-journal Peer-reviewed

    Yamamoto K, Shimizu A, Aizawa F, Kawame H, Tokutomi T, Fukushima A

    Journal of human genetics　63　(11)　1139-1147　2018/09

    DOI： 10.1038/s10038-018-0494-z 　

    ISSN： 1434-5161

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    Several biobanks have begun returning genetic results to individuals, making the development of public genetic literacy an urgent task for their effective use. No research exists regarding the effects of genetic education on biobank participants, so we conducted genetics workshops with specialists, and surveyed differences in the participants' (n = 112) preferences to receive their own genetic information by disease categories and their genetic knowledge using questionnaires before and after the workshops. Almost 90% of our participants were over 60 years old, which was similar to our previous preference research. The preference to receive five of the six categories of genetic information (lifestyle diseases, pharmacogenetics, adult-onset non-clinically actionable diseases, non-clinically actionable multifactorial diseases, and all genetic information) was slightly but significantly decreased after the genetics workshop. More participants preferred to receive genetic results regarding lifestyle diseases, pharmacogenetics, and adult-onset clinically actionable diseases after the workshop, while less participants preferred to receive information regarding adult-onset non-clinically actionable diseases, non-clinically actionable multifactorial diseases, and all genetic information. Total genetic knowledge scores significantly increased after the workshop (before: 11.89, after: 13.30, p < 0.001). Our findings suggest that genetics workshops are useful to improve the genetic literacy of genome cohort participants.

  114. Genome-wide analysis of polymorphism × sodium interaction effect on blood pressure identifies a novel 3'-BCL11B gene desert locus. International-journal Peer-reviewed

    Hachiya T, Narita A, Ohmomo H, Sutoh Y, Komaki S, Tanno K, Satoh M, Sakata K, Hitomi J, Nakamura M, Ogasawara K, Yamamoto M, Sasaki M, Hozawa A, Shimizu A

    Scientific reports　8　(1)　14162-14162　2018/09

    DOI： 10.1038/s41598-018-32074-1 　

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    Excessive sodium intake is a global risk factor for hypertension. Sodium effects on blood pressure vary from person to person; hence, high-risk group targeting based on personal genetic information can play a complementary role to ongoing population preventive approaches to reduce sodium consumption. To identify genetic factors that modulate sodium effects on blood pressure, we conducted a population-based genome-wide interaction analysis in 8,768 Japanese subjects, which was >3 times larger than a similar previous study. We tested 7,135,436 polymorphisms in the discovery cohort, and loci that met suggestive significance were further examined in an independent replication cohort. We found that an interaction between a novel 3'-BCL11B gene desert locus and daily sodium consumption was significantly associated with systolic blood pressure in both discovery and replication cohorts under the recessive model. Further statistical analysis of rs8022678, the sentinel variant of the 3'-BCL11B gene desert locus, showed that differences in mean systolic blood pressure between high and low sodium consumption subgroups were 5.9 mm Hg (P = 8.8 × 10-12) in rs8022678 A carriers and -0.3 mm Hg (P = 0.27) in rs8022678 A non-carriers, suggesting that the rs8022678 genotype can classify persons into sodium-sensitive (A carriers) and sodium-insensitive (A non-carriers) subgroups. Our results implied that rs8022678 A carriers may receive a greater benefit from sodium-lowering interventions than non-carriers.

  115. Genome-wide Association Study of Leisure-Time Exercise Behavior in Japanese Adults. International-journal Peer-reviewed

    Hara M, Hachiya T, Sutoh Y, Matsuo K, Nishida Y, Shimanoe C, Tanaka K, Shimizu A, Ohnaka K, Kawaguchi T, Oze I, Matsuda F, Ito H, Kawai S, Hishida A, Okada R, Sasakabe T, Hirata A, Ibusuki R, Nindita Y, Furusyo N, Ikezaki H, Kuriyama N, Ozaki E, Mikami H, Nakamura Y, Suzuki S, Hosono A, Katsuura-Kamano S, Arisawa K, Kuriki K, Endoh K, Takashima N, Kadota A, Nakatochi M, Momozawa Y, Kubo M, Naito M, Wakai K

    Medicine and science in sports and exercise　50　(12)　2433-2441　2018/08

    DOI： 10.1249/MSS.0000000000001712 　

    ISSN： 0195-9131

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    PURPOSE: Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. METHODS: We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. RESULTS: We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. CONCLUSIONS: We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

  116. 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.

  117. A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional espression International-journal Peer-reviewed

    C Shimanoe, T Hachiya, M Hara, Y Nishida, K Tanaka, Y Sutoh, A Shimizu, R Hishida, S Kawai, R Okada, T Tamura, K Matsuo, H Ito, E Ozaki, D Matsui, R Ibuseki, I Shimoshikiryo, N Takashima, A Kadota, Kokichi Arisawa, Hirokazu Uemura, S Suzuki, M Watanabe, K Kuriki, K Endoh, H Mikami, Y Nakamura, Y Momoxawa, M Kubo, M Nakatochi, M Naito, K Wakai

    Genes, Brain, and Behavior　18　(2)　e12481-e12481　2018/04/17

    DOI： 10.1111/gbb.12481 　

    ISSN： 1601-183X

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    Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant-level association evidence into gene-level evidence using a gene-based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability-scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10-6 ) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene-based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10-6 ). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.

  118. GWAS Identifies Two Novel Colorectal Cancer Loci at 16q24.1 and 20q13.12. International-journal Peer-reviewed

    Tanikawa C, Kamatani Y, Takahashi A, Momozawa Y, Leveque K, Nagayama S, Mimori K, Mori M, Ishii H, Inazawa J, Yasuda J, Tsuboi A, Shimizu A, Sasaki M, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Naito M, Wakai K, Koyama T, Takezaki T, Yuji K, Murakami Y, Nakamura Y, Kubo M, Matsuda K

    Carcinogenesis　39　(5)　652-660　2018/02

    DOI： 10.1093/carcin/bgy026 　

    ISSN： 0143-3334

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    Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Genome-wide association studies (GWAS) identified more than 50 CRC loci. However, most of the previous studies were conducted in European population, and host genetic factors among Japanese population are largely remained to be identified. To identify novel loci in the Japanese population, here, we performed a large-scale GWAS using 6692 cases and 27 178 controls followed by a replication analysis using more than 11 000 case-control samples. We found the significant association of 10 loci (P < 5 × 10-8), including 2 novel loci on 16q24.1 (IRF8-FOXF1, rs847208, P = 3.15 × 10-9 and odds ratio = 1.107 with 95% confidence interval (CI) of 1.071-1.145) and 20q13.12 (TOX2, rs6065668, P = 4.47 × 10-11 and odds ratio = 0.897 with 95% CI of 0.868-0.926). Moreover, 35 previously reported single nucleotide polymorphisms (SNPs) in 24 regions were validated in the Japanese population (P < 0.05) with the same risk allele as in the previous studies. SNP rs6065668 was significantly associated with TOX2 expression in the sigmoid colon. In addition, nucleotide substitutions in the regulatory region of TOX2 were predicted to alter the binding of several transcription factors, including KLF5. Our findings elucidate the important role of genetic variations in the development of CRC in the Japanese population.

  119. A Genome-wide Association Study in the Diabetic Patients Finds the 13q35.43-35.46 Locus Associated with Estimated Glomerular Filtration Rate: The Japan Multi-Institutional Collaborative Cohort Study Peer-reviewed

    Yasuyuki Nakamura, Akira Narita, Tsuyoshi Hachiya, Yoichi Sutoh, Atsushi Shimizu, Seiko Ohno, Naoyuki Takashima, Harumitsu Suzuki, Keitaro Tanaka, Megumi Hara, Kiyonori Kuriki, Kaori Endoh, Isao Oze, Hidemi Ito, Hirokazu Uemura, Sakurako Katsuura-Kamano, Haruo Mikami, Yohko Nakamura, Ippei Shimoshikiryo, Toshiro Takezaki, Sadao Suzuki, Miki Watanabe, Nagato Kuriyama, Teruhide Koyama, Norihiro Furusyo, Hiroaki Ikezaki, Masahiro Nakatochi, Sayo Kawai, Asahi Hishida, Rieko Okada, Takashi Tamura, Mariko Naito, Kenji Wakai, Yukihide Momozawa, Michiaki Kubo, Hirotsugu Ueshima, Yoshikuni Kita

    J Clin Diabetes 2018, 2:2　2　(2)　1-8　2018

  120. A Genome-wide Association Study in the Diabetic Patients Finds the 13q35.43-35.46 Locus Associated with Estimated Glomerular Filtration Rate: The Japan Multi-Institutional Collaborative Cohort Study Peer-reviewed

    Yasuyuki Nakamura, Akira Narita, Tsuyoshi Hachiya, Yoichi Sutoh, Atsushi Shimizu, Seiko Ohno, Naoyuki Takashima, Keitaro Tanaka, Megumi Hara, Kiyoshi Kuriki, Kaori Endoh, Isao Oze, Hidemi Ito, Hirokazu Uemura, Sakurako Katsuura-Kamano, Haruo Mikami, Yohko Nakamura, Ippei Shimoshikiryo, Toshiro Takezaki, Sadao Suzuki, Miki Watanabe, Nagato Kuriyama, Teruhide Koyama, Norihiro Furusyo, Hiroaki Ikezaki, Masahiro Nakatochi, Sayo Kawai, Asahi Hishida, Rieko Okada, Takashi Tamura, Mariko Naito, Kenji Wakai, Yukihide Momozawa, Michiaki Kubo, Hirotsugu Ueshima, Yoshikuni Kita

    Journal of Clinical Diabetes　Vol.2　(No.2)　102-102　2018

  121. 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

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

    Yodsurang V, Tang Y, Takahashi Y, Tanikawa C, Kamatani Y, Takahashi A, Momozawa Y, Fuse N, Sugawara J, Shimizu A, Fukushima A, Hishida A, Furusyo N, Naito M, Wakai K, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Hirata M, Murakami Y, Kubo M, Matsuda K

    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.

  123. iMETHYL: an integrative database of human DNA methylation, gene expression, and genomic variation. International-journal Peer-reviewed

    Komaki S, Shiwa Y, Furukawa R, Hachiya T, Ohmomo H, Otomo R, Satoh M, Hitomi J, Sobue K, Sasaki M, Shimizu A

    Human genome variation　5　18008-18008　2018

    DOI： 10.1038/hgv.2018.8 　

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    We launched an integrative multi-omics database, iMETHYL (http://imethyl.iwate-megabank.org). iMETHYL provides whole-DNA methylation (~24 million autosomal CpG sites), whole-genome (~9 million single-nucleotide variants), and whole-transcriptome (>14 000 genes) data for CD4+ T-lymphocytes, monocytes, and neutrophils collected from approximately 100 subjects. These data were obtained from whole-genome bisulfite sequencing, whole-genome sequencing, and whole-transcriptome sequencing, making iMETHYL a comprehensive database.

  124. Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA(1c) Peer-reviewed

    Tsuyoshi Hachiya, Shohei Komaki, Yutaka Hasegawa, Hideki Ohmomo, Kozo Tanno, Atsushi Hozawa, Gen Tamiya, Masayuki Yamamoto, Kuniaki Ogasawara, Motoyuki Nakamura, Jiro Hitomi, Yasushi Ishigaki, Makoto Sasaki, Atsushi Shimizu

    SCIENTIFIC REPORTS　7　(1)　16147　2017/11

    DOI： 10.1038/s41598-017-16493-0 　

    ISSN： 2045-2322

  125. An epigenome-wide association study based on cell type-specific whole-genome bisulfite sequencing: Screening for DNA methylation signatures associated with bone mass Peer-reviewed

    Komaki, S, Ohmomo, H, Hachiya, T, Furukawa, R, Shiwa, Y, Satoh, M, Endo, R, Doita, M, Sasaki, M, Shimizu, A

    Integrative Molecular Medicine　4　(5)　2017/10

    Publisher: Open Access Text Pvt, Ltd.

    DOI： 10.15761/imm.1000307 　

    eISSN： 2056-6360

  126. Genome-wide association study identifies 112 new loci for body mass index in the Japanese population Peer-reviewed

    Masato Akiyama, Yukinori Okada, Masahiro Kanai, Atsushi Takahashi, Yukihide Momozawa, Masashi Ikeda, Nakao Iwata, Shiro Ikegawa, Makoto Hirata, Koichi Matsuda, Motoki Iwasaki, Taiki Yamaji, Norie Sawada, Tsuyoshi Hachiya, Kozo Tanno, Atsushi Shimizu, Atsushi Hozawa, Naoko Minegishi, Shoichiro Tsugane, Masayuki Yamamoto, Michiaki Kubo, Yoichiro Kamatani

    NATURE GENETICS　49　(10)　1458-+　2017/10

    DOI： 10.1038/ng.3951 　

    ISSN： 1061-4036

    eISSN： 1546-1718

  127. Clonal analysis of construction mechanism of the adult telencephalon mediated by post-hatch neurogenesiss in medaka fish Peer-reviewed

    Yasuko Isoe, Ryohei Nakamura, Yasuhiro Kamei, Shigenori Nonaka, Teruhiro Okuyama, Atsushi Shimizu, Takeo Kubo, Hiroyuki Takeda, Hideaki Takeuchi

    Mechanisms of Development　145　S118-S119　2017/07

    DOI： 10.1016/j.mod.2017.04.320 　

    ISSN： 0925-4773

    eISSN： 1872-6356

  128. f-treeGC: a questionnaire-based family treecreation software for genetic counseling and genome cohort studies Peer-reviewed

    Tomoharu Tokutomi, Akimune Fukushima, Kayono Yamamoto, Yasushi Bansho, Tsuyoshi Hachiya, Atsushi Shimizu

    BMC MEDICAL GENETICS　18　(1)　71　2017/07

    DOI： 10.1186/s12881-017-0433-4 　

    ISSN： 1471-2350

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

    Shinichi Kuriyama, Nobuo Yaegashi, Fuji Nagami, Tomohiko Arai, Yoshio Kawaguchi, Noriko Osumi, Masaki Sakaida, Yoichi Suzuki, Keiko Nakayama, Hiroaki Hashizume, Gen Tamiya, Hiroshi Kawame, Kichiya Suzuki, Atsushi Hozawa, Naoki Nakaya, Masahiro Kikuya, Hirohito Metoki, Ichiro Tsuji, Nobuo Fuse, Hideyasu Kiyomoto, Junichi Sugawara, Akito Tsuboi, Shinichi Egawa, Kiyoshi Ito, Koichi Chida, Tadashi Ishii, Hiroaki Tomita, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Jun Yasuda, Kazuhiko Igarashi, Ritsuko Shimizu, Masao Nagasaki, Seizo Koshiba, Kengo Kinoshita, Soichi Ogishima, Takako Takai-Igarashi, Teiji Tominaga, Osamu Tanabe, Noriaki Ohuchi, Toru Shimosegawa, Shigeo Kure, Hiroshi Tanaka, Sadayoshi Ito, Jiro Hitomi, Kozo Tanno, Motoyuki Nakamura, Kuniaki Ogasawara, Seiichiro Kobayashi, Kiyomi Sakata, Mamoru Satoh, Atsushi Shimizu, Makoto Sasaki, Ryujin Endo, Kenji Sobue, Masayuki Yamamoto

    JOURNAL OF EPIDEMIOLOGY　26　(9)　493-511　2016/09

    DOI： 10.2188/jea.JE20150268 　

    ISSN： 0917-5040

  130. SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. International-journal

    Satoshi Narumi, Naoko Amano, Tomohiro Ishii, Noriyuki Katsumata, Koji Muroya, Masanori Adachi, Katsuaki Toyoshima, Yukichi Tanaka, Ryuji Fukuzawa, Kenichi Miyako, Saori Kinjo, Shouichi Ohga, Kenji Ihara, Hirosuke Inoue, Tadamune Kinjo, Toshiro Hara, Miyuki Kohno, Shiro Yamada, Hironaka Urano, Yosuke Kitagawa, Koji Tsugawa, Asumi Higa, Masakazu Miyawaki, Takahiro Okutani, Zenro Kizaki, Hiroyuki Hamada, Minako Kihara, Kentaro Shiga, Tetsuya Yamaguchi, Manabu Kenmochi, Hiroyuki Kitajima, Maki Fukami, Atsushi Shimizu, Jun Kudoh, Shinsuke Shibata, Hideyuki Okano, Noriko Miyake, Naomichi Matsumoto, Tomonobu Hasegawa

    Nature genetics　48　(7)　792-7　2016/07

    DOI： 10.1038/ng.3569 　

    ISSN： 1546-1718

    More details Close

    Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.

  131. SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7 Peer-reviewed

    Satoshi Narumi, Naoko Amano, Tomohiro Ishii, Noriyuki Katsumata, Koji Muroya, Masanori Adachi, Katsuaki Toyoshima, Yukichi Tanaka, Ryuji Fukuzawa, Kenichi Miyako, Saori Kinjo, Shouichi Ohga, Kenji Ihara, Hirosuke Inoue, Tadamune Kinjo, Toshiro Hara, Miyuki Kohno, Shiro Yamada, Hironaka Urano, Yosuke Kitagawa, Koji Tsugawa, Asumi Higa, Masakazu Miyawaki, Takahiro Okutani, Zenro Kizaki, Hiroyuki Hamada, Minako Kihara, Kentaro Shiga, Tetsuya Yamaguchi, Manabu Kenmochi, Hiroyuki Kitajima, Maki Fukami, Atsushi Shimizu, Jun Kudoh, Shinsuke Shibata, Hideyuki Okano, Noriko Miyake, Naomichi Matsumoto, Tomonobu Hasegawa

    NATURE GENETICS　48　(7)　792-+　2016/07

    DOI： 10.1038/ng.3569 　

    ISSN： 1061-4036

    eISSN： 1546-1718

  132. Tumour resistance in induced pluripotent stem cells derived from naked mole-rats Peer-reviewed

    Shingo Miyawaki, Yoshimi Kawamura, Yuki Oiwa, Atsushi Shimizu, Tsuyoshi Hachiya, Hidemasa Bono, Ikuko Koya, Yohei Okada, Tokuhiro Kimura, Yoshihiro Tsuchiya, Sadafumi Suzuki, Nobuyuki Onishi, Naoko Kuzumaki, Yumi Matsuzaki, Minoru Narita, Eiji Ikeda, Kazuo Okanoya, Ken-ichiro Seino, Hideyuki Saya, Hideyuki Okano, Kyoko Miura

    NATURE COMMUNICATIONS　7　11471　2016/05

    DOI： 10.1038/ncomms11471 　

    ISSN： 2041-1723

  133. Progress of Japanese omics reference panels in iwate tohoku medical megabank project Peer-reviewed

    Ryohei Furukawa, Atsushi Shimizu

    Seikagaku　88　(1)　36-43　2016

    Publisher: Japanese Biochemical Society

    DOI： 10.14952/SEIKAGAKU.2016.880036 　

    ISSN： 2189-0544 0037-1017

  134. Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols Peer-reviewed

    Yuh Shiwa, Tsuyoshi Hachiya, Ryohei Furukawa, Hideki Ohmomo, Kanako Ono, Hisaaki Kudo, Jun Hata, Atsushi Hozawa, Motoki Iwasaki, Koichi Matsuda, Naoko Minegishi, Mamoru Satoh, Kozo Tanno, Taiki Yamaji, Kenji Wakai, Jiro Hitomi, Yutaka Kiyohara, Michiaki Kubo, Hideo Tanaka, Shoichiro Tsugane, Masayuki Yamamoto, Kenji Sobue, Atsushi Shimizu

    PLOS ONE　11　(1)　e0147519　2016/01

    DOI： 10.1371/journal.pone.0147519 　

    ISSN： 1932-6203

  135. Targeted next-generation sequencing in the diagnosis of neurodevelopmental disorders Peer-reviewed

    N. Okamoto, F. Miya, T. Tsunoda, M. Kato, S. Saitoh, M. Yamasaki, A. Shimizu, C. Torii, Y. Kanemura, K. Kosaki

    CLINICAL GENETICS　88　(3)　288-292　2015/09

    DOI： 10.1111/cge.12492 　

    ISSN： 0009-9163

    eISSN： 1399-0004

  136. 次世代シークエンサーと解析パネルを用いたNF1遺伝子診断法の構築 Peer-reviewed

    丸岡 亮, 武内 俊樹, 清水 厚志, 鳥居 千春, 三須 久美子, 日笠 幸一郎, 松田 文彦, 太田 有史, 谷戸 克己, 倉持 朗, 有馬 好美, 大塚 藤男, 吉田 雄一, 森山 啓司, 小崎 里華, 新村 眞人, 佐谷 秀行, 小崎 健次郎

    日本レックリングハウゼン病学会雑誌　6　(1)　79-79　2015/04

    Publisher: 日本レックリングハウゼン病学会

    ISSN： 2185-5773

  137. Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition Peer-reviewed

    Satoshi Nori, Yohei Okada, Soraya Nishimura, Takashi Sasaki, Go Itakura, Yoshiomi Kobayashi, Francois Renault-Mihara, Atsushi Shimizu, Ikuko Koya, Rei Yoshida, Jun Kudoh, Masato Koike, Yasuo Uchiyama, Eiji Ikeda, Yoshiaki Toyama, Masaya Nakamura, Hideyuki Okano

    STEM CELL REPORTS　4　(3)　360-373　2015/03

    DOI： 10.1016/j.stemcr.2015.01.006 　

    ISSN： 2213-6711

  138. Molecular cloning and characterization of the Ink4a and ARF genes in naked mole-rat Peer-reviewed

    Miyawaki S, Kawamura Y, Hachiya T, Shimizu A, Miura K

    Inflammation and Regeneration　35　(1)　42-50　2015/02

    Publisher: The Japanese Society of Inflammation and Regeneration

    DOI： 10.2492/inflammregen.35.042 　

    ISSN： 1880-9693

    More details Close

    The naked mole-rat (NMR) is the world's longest-living rodent, with a maximum lifespan of longer than 31 years without any evidence of neoplastic disease. Recently, the NMR has come to be regarded as a useful animal model for the study of longevity and cancer resistance. Sequencing analysis of the NMR genome revealed the existence of species-specific changes in the predicted sequence of the INK4a and ARF tumor suppressors, suggesting the possibility that these two genes might have important roles in NMR's unique longevity and cancer resistance. Here, we report the molecular cloning and characterization of the INK4a and ARF genes in vitro. To investigate the expression and function of the INK4a and ARF genes in NMR, we generated several research tools, including antibodies, real-time PCR primer sets, and overexpression and knockdown vectors. Our results showed that endogenous expression of INK4a and ARF was upregulated in NMR fibroblasts treated with DNA-damaging agents or after serial passaging. In addition, overexpression of INK4a or ARF caused cell cycle arrest in both NMR fibroblasts and mouse NIH-3T3 cells. These results suggest INK4a and ARF execute a conserved function as cell cycle inhibitors in NMR. The research tools developed in the present study will be useful for exploring the specific function of INK4a and ARF genes in the unique longevity and cancer-resistant phenotype of NMRs.

  139. The use of next-generation sequencing in molecular diagnosis of neurofibromatosis type 1: a validation study. International-journal

    Maruoka R, Takenouchi T, Torii C, Shimizu A, Misu K, Higasa K, Matsuda F, Ota A, Tanito K, Kuramochi A, Arima Y, Otsuka F, Yoshida Y, Moriyama K, Niimura M, Saya H, Kosaki K

    Genet Test Mol Biomarkers　18　(11)　722-735　2014/11

    DOI： 10.1089/gtmb.2014.0109 　

    ISSN： 1945-0257

    More details Close

    We assessed the validity of a next-generation sequencing protocol using in-solution hybridization-based enrichment to identify NF1 mutations for the diagnosis of 86 patients with a prototypic genetic syndrome, neurofibromatosis type 1. In addition, other causative genes for classic genetic syndromes were set as the target genes for coverage analysis.<br /> The protocol identified 30 nonsense, 19 frameshift, and 8 splice-site mutations, together with 10 nucleotide substitutions that were previously reported to be pathogenic. In the remaining 19 samples, 10 had single-exon or multiple-exon deletions detected by a multiplex ligation-dependent probe amplification method and 3 had missense mutations that were not observed in the normal Japanese SNP database and were predicted to be pathogenic. Coverage analysis of the genes other than the NF1 gene included on the same diagnostic panel indicated that the mean coverage was 115-fold, a sufficient depth for mutation detection.<br /> The overall mutation detection rate using the currently reported method in 86 patients who met the clinical diagnostic criteria was 92.1% (70/76) when 10 patients with large deletions were excluded. The results validate the

  140. The Use of Next-Generation Sequencing in Molecular Diagnosis of Neurofibromatosis Type 1: A Validation Study Peer-reviewed

    Ryo Maruoka, Toshiki Takenouchi, Chiharu Torii, Atsushi Shimizu, Kumiko Misu, Koichiro Higasa, Fumihiko Matsuda, Arihito Ota, Katsumi Tanito, Akira Kuramochi, Yoshimi Arima, Fujio Otsuka, Yuichi Yoshida, Keiji Moriyama, Michihito Niimura, Hideyuki Saya, Kenjiro Kosaki

    GENETIC TESTING AND MOLECULAR BIOMARKERS　18　(11)　722-735　2014/11

    DOI： 10.1089/gtmb.2014.0109 　

    ISSN： 1945-0265

    eISSN： 1945-0257

  141. Global gene expression analysis following spinal cord injury in non-human primates Peer-reviewed

    Soraya Nishimura, Takashi Sasaki, Atsushi Shimizu, Kenji Yoshida, Hiroki Iwai, Ikuko Koya, Yoshiomi Kobayashi, Go Itakura, Shinsuke Shibata, Hayao Ebise, Keisuke Horiuchi, Jun Kudoh, Yoshiaki Toyama, Aileen J. Anderson, Hideyuki Okano, Masaya Nakamura

    EXPERIMENTAL NEUROLOGY　261　171-179　2014/11

    DOI： 10.1016/j.expneurol.2014.05.021 　

    ISSN： 0014-4886

    eISSN： 1090-2430

  142. Dramatic improvement in genome assembly achieved using doubled-haploid genomes Peer-reviewed

    Hong Zhang, Engkong Tan, Yutaka Suzuki, Yusuke Hirose, Shigeharu Kinoshita, Hideyuki Okano, Jun Kudoh, Atsushi Shimizu, Kazuyoshi Saito, Shugo Watabe, Shuichi Asakawa

    SCIENTIFIC REPORTS　4　6780　2014/10

    DOI： 10.1038/srep06780 　

    ISSN： 2045-2322

  143. Reduction of Systematic Bias in Transcriptome Data from Human Peripheral Blood Mononuclear Cells for Transportation and Biobanking Peer-reviewed

    Hideki Ohmomo, Tsuyoshi Hachiya, Yu Shiwa, Ryohei Furukawa, Kanako Ono, Shigeki Ito, Yoji Ishida, Mamoru Satoh, Jiro Hitomi, Kenji Sobue, Atsushi Shimizu

    PLOS ONE　9　(8)　e104283　2014/08

    DOI： 10.1371/journal.pone.0104283 　

    ISSN： 1932-6203

  144. Sox5 Functions as a Fate Switch in Medaka Pigment Cell Development Peer-reviewed

    Yusuke Nagao, Takao Suzuki, Atsushi Shimizu, Tetsuaki Kimura, Ryoko Seki, Tomoko Adachi, Chikako Inoue, Yoshihiro Omae, Yasuhiro Kamei, Ikuyo Hara, Yoshihito Taniguchi, Kiyoshi Naruse, Yuko Wakamatsu, Robert N. Kelsh, Masahiko Hibi, Hisashi Hashimoto

    PLOS GENETICS　10　(4)　2014/04

    DOI： 10.1371/journal.pgen.1004246 　

    ISSN： 1553-7404

  145. Multiple Cafe au Lait Spots in Familial Patients With MAP2K2 Mutation Peer-reviewed

    Toshiki Takenouchi, Atsushi Shimizu, Chiharu Torii, Rika Kosaki, Takao Takahashi, Hideyuki Saya, Kenjiro Kosaki

    AMERICAN JOURNAL OF MEDICAL GENETICS PART A　164　(2)　392-396　2014/02

    DOI： 10.1002/ajmg.a.36288 　

    ISSN： 1552-4825

    eISSN： 1552-4833

  146. Global gene expression analysis following spinal cord injury in non-human primates

    Soraya Nishimura, Takashi Sasaki, Atsushi Shimizu, Kenji Yoshida, Hiroki Iwai, Ikuko Koya, Yoshiomi Kobayashi, Go Itakura, Shinsuke Shibata, Hayao Ebise, Keisuke Horiuchi, Jun Kudoh, Yoshiaki Toyama, Aileen J. Anderson, Hideyuki Okano, Masaya Nakamura

    Experimental Neurology　261　171-179　2014

    Publisher: Academic Press Inc.

    DOI： 10.1016/j.expneurol.2014.05.021 　

    ISSN： 1090-2430 0014-4886

  147. Sox5 Functions as a Fate Switch in Medaka Pigment Cell Development Peer-reviewed

    Yusuke Nagao, Takao Suzuki, Atsushi Shimizu, Tetsuaki Kimura, Ryoko Seki, Tomoko Adachi, Chikako Inoue, Yoshihiro Omae, Yasuhiro Kamei, Ikuyo Hara, Yoshihito Taniguchi, Kiyoshi Naruse, Yuko Wakamatsu, Robert N. Kelsh, Masahiko Hibi, Hisashi Hashimoto

    PLoS Genetics　10　(4)　e1004246　2014

    Publisher: Public Library of Science

    DOI： 10.1371/journal.pgen.1004246 　

    ISSN： 1553-7404 1553-7390

  148. Mutations in SERPINB7, Encoding a Member of the Serine Protease Inhibitor Superfamily, Cause Nagashima-type Palmoplantar Keratosis Peer-reviewed

    Akiharu Kubo, Aiko Shiohama, Takashi Sasaki, Kazuhiko Nakabayashi, Hiroshi Kawasaki, Toru Atsugi, Showbu Sato, Atsushi Shimizu, Shuji Mikami, Hideaki Tanizaki, Masaki Uchiyama, Tatsuo Maeda, Taisuke Ito, Jun-ichi Sakabe, Toshio Heike, Torayuki Okuyama, Rika Kosaki, Kenjiro Kosaki, Jun Kudoh, Kenichiro Hata, Akihiro Umezawa, Yoshiki Tokura, Akira Ishiko, Hironori Niizeki, Kenji Kabashima, Yoshihiko Mitsuhashi, Masayuki Amagai

    AMERICAN JOURNAL OF HUMAN GENETICS　93　(5)　945-956　2013/11

    DOI： 10.1016/j.ajhg.2013.09.015 　

    ISSN： 0002-9297

    eISSN： 1537-6605

  149. A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis Peer-reviewed

    Takashi Sasaki, Aiko Shiohama, Akiharu Kubo, Hiroshi Kawasaki, Akemi Ishida-Yamamoto, Taketo Yamada, Takayuki Hachiya, Atsushi Shimizu, Hideyuki Okano, Jun Kudoh, Masayuki Amagai

    Journal of Allergy and Clinical Immunology　132　(5)　1111-e4　2013/11

    Publisher: 5

    DOI： 10.1016/j.jaci.2013.08.027 　

    ISSN： 0091-6749 1097-6825

  150. Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study

    Hideki Mutai, Naohiro Suzuki, Atsushi Shimizu, Chiharu Torii, Kazunori Namba, Noriko Morimoto, Jun Kudoh, Kimitaka Kaga, Kenjiro Kosaki, Tatsuo Matsunaga

    ORPHANET JOURNAL OF RARE DISEASES　8　(1)　2013/10

    DOI： 10.1186/1750-1172-8-172 　

    ISSN： 1750-1172

  151. Assessment of homozygosity levels in the mito-gynogenetic torafugu (Takifugu rubripes) by genome-wide SNP analyses Peer-reviewed

    Hong Zhang, Yusuke Hirose, Rintaro Yoshino, Shigeharu Kinoshita, Kazuyoshi Saito, Engkong Tan, Yutaka Suzuki, Atsushi Shimizu, Hideyuki Okano, Jun Kudoh, Shugo Watabe, Shuichi Asakawa

    Aquaculture　380-383　114-119　2013/03/04

    DOI： 10.1016/j.aquaculture.2012.12.003 　

    ISSN： 0044-8486

  152. Establishment of HRASG12V Transgenic Medaka as a Stable Tumor Model for In Vivo Screening of Anticancer Drugs

    Yuriko Matsuzaki, Haru Hosokai, Yukiyo Mizuguchi, Shoji Fukamachi, Atsushi Shimizu, Hideyuki Saya

    PLoS ONE　8　(1)　2013/01/14

    DOI： 10.1371/journal.pone.0054424 　

    ISSN： 1932-6203

  153. Dual promoter expression system with insulator ensures a stringent tissue-specific regulation of two reporter genes in the transgenic fish Peer-reviewed

    Atsushi Shimizu, Nobuyoshi Shimizu

    Transgenic Research　22　(2)　435-444　2013

    Publisher: 2

    DOI： 10.1007/s11248-012-9653-8 　

    ISSN： 0962-8819

  154. Identification of mutations in the prostaglandin transporter gene SLCO2A1 and its phenotype-genotype correlation in Japanese patients with pachydermoperiostosis

    Takashi Sasaki, Hironori Niizeki, Atsushi Shimizu, Aiko Shiohama, Asami Hirakiyama, Torayuki Okuyama, Atsuhito Seki, Kenji Kabashima, Atsushi Otsuka, Akira Ishiko, Keiji Tanese, Shun-ichi Miyakawa, Jun-ichi Sakabe, Masamitsu Kuwahara, Masayuki Amagai, Hideyuki Okano, Makoto Suematsu, Jun Kudoh

    JOURNAL OF DERMATOLOGICAL SCIENCE　68　(1)　36-44　2012/10

    DOI： 10.1016/j.jdermsci.2012.07.008 　

    ISSN： 0923-1811

    eISSN： 1873-569X

  155. Restoration of the intrinsic properties of human dermal papilla in vitro

    Manabu Ohyama, Tetsuro Kobayashi, Takashi Sasaki, Atsushi Shimizu, Masayuki Amagai

    JOURNAL OF CELL SCIENCE　125　(17)　4114-4125　2012/09

    DOI： 10.1242/jcs.105700 　

    ISSN： 0021-9533

  156. The Medaka zic1/zic4 Mutant Provides Molecular Insights into Teleost Caudal Fin Evolution Peer-reviewed

    Yuuta Moriyama, Toru Kawanishi, Ryohei Nakamura, Tatsuya Tsukahara, Kenta Sumiyama, Maximiliano L. Suster, Koichi Kawakami, Atsushi Toyoda, Asao Fujiyama, Yuuri Yasuoka, Yusuke Nagao, Etsuko Sawatari, Atsushi Shimizu, Yuko Wakamatsu, Masahiko Hibi, Masanori Taira, Masataka Okabe, Kiyoshi Naruse, Hisashi Hashimoto, Atsuko Shimada, Hiroyuki Takeda

    CURRENT BIOLOGY　22　(7)　601-607　2012/04

    DOI： 10.1016/j.cub.2012.01.063 　

    ISSN： 0960-9822

  157. Insufficiency of BUBR1, a mitotic spindle checkpoint regulator, causes impaired ciliogenesis in vertebrates Peer-reviewed

    Tatsuo Miyamoto, Sean Porazinski, Huijia Wang, Antonia Borovina, Brian Ciruna, Atsushi Shimizu, Tadashi Kajii, Akira Kikuchi, Makoto Furutani-Seiki, Shinya Matsuura

    HUMAN MOLECULAR GENETICS　20　(10)　2058-2070　2011/05

    DOI： 10.1093/hmg/ddr090 　

    ISSN： 0964-6906

  158. インハウスのプリントBACマイクロアレイを用いた四つの腫瘍タイプのゲノム不安定性解析(Genomic Instability Analysis of Four Tumor Types Using In-house Printed BAC-Microarray)

    村山 裕治, 高柳 淳, 清水 厚志, 小澤 壯治, 浅川 修一, 才川 義朗, 長谷川 博俊, 神野 浩光, 相浦 浩一, 前川 雅彦, 工藤 純, 北川 雄光, 北島 政樹, 清水 信義

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　83回・33回　3P-0967　2010/12

    Publisher: (公社)日本生化学会

  159. YPEL5 protein of the YPEL gene family is involved in the cell cycle progression by interacting with two distinct proteins RanBPM and RanBP10 Peer-reviewed

    Katsuhiro Hosono, Setsuko Noda, Atsushi Shimizu, Nobuo Nakanishi, Masafumi Ohtsubo, Nobuyoshi Shimizu, Shinsei Minoshima

    GENOMICS　96　(2)　102-111　2010/08

    DOI： 10.1016/j.ygeno.2010.05.003 　

    ISSN： 0888-7543

    eISSN： 1089-8646

  160. Hyper-expansion of large DNA segments in the genome of kuruma shrimp, Marsupenaeus japonicus Peer-reviewed

    Koyama Takashi, Asakawa Shuichi, Katagiri Takayuki, Shimizu Atsushi, Fagutao Fernand F, Mavichak Rapeepat, Santos Mudjekeewis D, Fuji Kanako, Sakamoto Takashi, Kitakado Toshihide, Kondo Hidehiro, Shimizu Nobuyoshi, Aoki Takashi, Hirono Ikuo

    BMC GENOMICS　11　2010/02/26

    DOI： 10.1186/1471-2164-11-141 　

    ISSN： 1471-2164

  161. Analysis of eighteen deletion breakpoints in the parkin gene Peer-reviewed

    Shuichi Asakawa, Nobutaka Hattori, Atsushi Shimizu, Yoshiko Shimizu, Shinsei Minoshima, Yoshikuni Mizuno, Nobuyoshi Shimizu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　389　(1)　181-186　2009/11

    DOI： 10.1016/j.bbrc.2009.08.115 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  162. Sequence analysis of filaggrin gene by novel shotgun method in Japanese atopic dermatitis Peer-reviewed

    Takashi Sasaki, Jun Kudoh, Tamotsu Ebihara, Aiko Shiohama, Shuichi Asakawa, Atsushi Shimizu, Atsushi Takayanagi, Itaru Dekio, Chieko Sadahira, Masayuki Amagai, Nobuyoshi Shimizu

    JOURNAL OF DERMATOLOGICAL SCIENCE　51　(2)　113-120　2008/08

    DOI： 10.1016/j.jdermsci.2008.02.009 　

    ISSN： 0923-1811

  163. UTGB/medaka: Genomic resource database for medaka biology

    Budrul Ahsan, Daisuke Kobayashi, Tomoyuki Yamada, Masahiro Kasahara, Shin Sasaki, Taro I. Saito, Yukinobu Nagayasu, Koichiro Doi, Yoichiro Nakatani, Wei Qu, Tomoko Jindo, Atsuko Shimada, Kiyoshi Naruse, Atsushi Toyoda, Yoko Kuroki, Asao Fujiyama, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Nobuyoshi Shimizu, Shin-Ichi Hashimoto, Jun Yang, Yongjun Lee, Kouji Matsushima, Sumio Sugano, Mitsuru Sakaizumi, Takanori Narita, Kazuko Ohishi, Shinobu Haga, Fumiko Ohta, Hisayo Nomoto, Keiko Nogata, Tomomi Morishita, Tomoko Endo, Tadasu Shin-i, Hiroyuki Takeda, Yuji Kohara, Shinichi Morishita

    Nucleic Acids Research　36　(1)　D747-D752　2008/01

    DOI： 10.1093/nar/gkm765 　

    ISSN： 0305-1048 1362-4962

    eISSN： 1362-4962

  164. UTGB/medaka: genomic resource database for medaka biology Peer-reviewed

    Budrul Ahsan, Daisuke Kobayashi, Tomoyuki Yamada, Masahiro Kasahara, Shin Sasaki, Taro L. Saito, Yukinobu Nagayasu, Koichiro Doi, Yoichiro Nakatani, Wei Qu, Tomoko Jindo, Atsuko Shimada, Kiyoshi Naruse, Atsushi Toyoda, Yoko Kuroki, Asao Fujiyama, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Nobuyoshi Shimizu, Shin-Ichi Hashimoto, Jun Yang, Yongjun Lee, Kouji Matsushima, Sumio Sugano, Mitsuru Sakaizumi, Takanori Narita, Kazuko Ohishi, Shinobu Haga, Fumiko Ohta, Hisayo Nomoto, Keiko Nogata, Tomomi Morishita, Tomoko Endo, Tadasu Shin-I, Hiroyuki Takeda, Yuji Kohara, Shinichi Morishita

    NUCLEIC ACIDS RESEARCH　36　D747-D752　2008/01

    DOI： 10.1093/nar/gkm765 　

    ISSN： 0305-1048

  165. Myocyte enhancer factor 2 regulates expression of medaka Oryzias latipes fast skeletal myosin heavy chain genes in a temperature-dependent manner Peer-reviewed

    Chun-Shi Liang, Daisuke Ikeda, Shigeharu Kinoshita, Atsushi Shimizu, Takashi Sasaki, Shuichi Asakawa, Nobuyoshi Shimizu, Shugo Watabe

    GENE　407　(1-2)　42-53　2008/01

    DOI： 10.1016/j.gene.2007.09.016 　

    ISSN： 0378-1119

  166. The medaka draft genome and insights into vertebrate genome evolution

    Masahiro Kasahara, Kiyoshi Naruse, Shin Sasaki, Yoichiro Nakatani, Wei Qu, Budrul Ahsan, Tomoyuki Yamada, Yukinobu Nagayasu, Koichiro Doi, Yasuhiro Kasai, Tomoko Jindo, Daisuke Kobayashi, Atsuko Shimada, Atsushi Toyoda, Yoko Kuroki, Asao Fujiyama, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Nobuyoshi Shimizu, Shin-Ichi Hashimoto, Jun Yang, Yongjun Lee, Kouji Matsushima, Sumio Sugano, Mitsuru Sakaizumi, Takanori Narita, Kazuko Ohishi, Shinobu Haga, Fumiko Ohta, Hisayo Nomoto, Keiko Nogata, Tomomi Morishita, Tomoko Endo, Tadasu Shin-I, Hiroyuki Takeda, Shinichi Morishita, Yuji Kohara

    Nature　447　(7145)　714-719　2007/06/07

    Publisher: Nature Publishing Group

    DOI： 10.1038/nature05846 　

    ISSN： 1476-4687 0028-0836

    eISSN： 1476-4687

  167. The medaka draft genome and insights into vertebrate genome evolution Peer-reviewed

    Masahiro Kasahara, Kiyoshi Naruse, Shin Sasaki, Yoichiro Nakatani, Wei Qu, Budrul Ahsan, Tomoyuki Yamada, Yukinobu Nagayasu, Koichiro Doi, Yasuhiro Kasai, Tomoko Jindo, Daisuke Kobayashi, Atsuko Shimada, Atsushi Toyoda, Yoko Kuroki, Asao Fujiyama, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Nobuyoshi Shimizu, Shin-ichi Hashimoto, Jun Yang, Yongjun Lee, Kouji Matsushima, Sumio Sugano, Mitsuru Sakaizumi, Takanori Narita, Kazuko Ohishi, Shinobu Haga, Fumiko Ohta, Hisayo Nomoto, Keiko Nogata, Tomomi Morishita, Tomoko Endo, Tadasu Shin-, Hiroyuki Takeda, Shinichi Morishita, Yuji Kohara

    NATURE　447　(7145)　714-719　2007/06

    DOI： 10.1038/nature05846 　

    ISSN： 0028-0836

  168. Radiation hybrid maps of Medaka chromosomes LG 12, 17, and 22 Peer-reviewed

    Feng Su, Yumi Osada, Marc Ekker, Mario Chevrette, Atsushi Shimizu, Shuichi Asakawa, Aiko Shiohama, Takashi Sasaki, Nobuyoshi Shimizu, Toshiyuki Yamanaka, Takao Sasado, Hiroshi Mitani, Robert Geisler, Hisato Kondoh, Makoto Furutani-Seiki

    DNA RESEARCH　14　(3)　135-140　2007/06

    DOI： 10.1093/dnares/dsm012 　

    ISSN： 1340-2838

  169. Fast skeletal muscle myosin heavy chain gene cluster of medaka Oryzias latipes enrolled in temperature adaptation

    Liang, C. S, Kobiyama, A, Shimizu, A, Sasaki, T, Asakawa, S, Shimizu, N, Watabe, S

    Physiol Genomics　29　(2)　201-14　2007/04/24

    DOI： 10.1152/physiolgenomics.00078.2006 　

    ISSN： 1531-2267

    More details Close

    To disclose mechanisms involved in temperature acclimation of fish muscle, we subjected eurythermal fish of medaka Oryzias latipes to cloning of myosin heavy chain genes (MYHs). We cloned cDNAs encoding fast skeletal muscle myosin heavy chain (MYH) isoforms from cDNA libraries of medaka acclimated to 10 and 30 degrees C and observed that different MYH cDNA clones are expressed in the two temperature-acclimated fish. Subsequently, we isolated several overlapping MYH contigs by shotgun cloning strategy from a medaka genomic library. Contig assembly of the complete medaka MYH (mMYH) locus of 219 kbp revealed a cluster of tandemly arrayed 11 mMYHs, in which eight genes are actually transcribed, with the remaining three being pseudogenes. Expression analysis of the transcribed genes revealed that two genes were each highly expressed in medaka acclimated to 10 and 30 degrees C, whereas comparatively lower expression levels of the three genes were exclusively observed in medaka acclimated to 30 degrees C. cDNAs of the remaining genes were too underrepresented in the libraries to determine the expression levels, and the transcripts could only be obtained by reverse transcription-polymerase

  170. Fast skeletal muscle myosin heavy chain gene cluster of medaka Oryzias latipes enrolled in temperature adaptation Peer-reviewed

    Chun-Shi Liang, Atsushi Kobiyama, Atsushi Shimizu, Takashi Sasaki, Shuichi Asakawa, Nobuyoshi Shimizu, Shugo Watabe

    PHYSIOLOGICAL GENOMICS　29　(2)　201-214　2007/04

    DOI： 10.1152/physiolgenomics.00078.2006 　

    ISSN： 1094-8341

  171. The genome size evolution of medaka (Oryzias latipes) and fugu (Takifugu rubripes) Peer-reviewed

    Shuichiro Imai, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Hiroshi Hori, Nobuyoshi Shimizu

    GENES & GENETIC SYSTEMS　82　(2)　135-144　2007/04

    DOI： 10.1266/ggs.82.135 　

    ISSN： 1341-7568

    eISSN： 1880-5779

  172. The DNA sequence of medaka chromosome LG22 Peer-reviewed

    Takashi Sasaki, Atsushi Shimizu, Sabine K. Ishikawa, Shuichiro Imai, Shuichi Asakawa, Yuji Murayama, Maryam Zadeh Khorasani, Hiroshi Mitani, Makoto Furutani-Seiki, Hisato Kondoh, Indrajit Nanda, Michael Schmid, Manfred Schartl, Masaru Nonaka, Hiroyuki Takeda, Hiroshi Hori, Heinz Himmelbauer, Akihiro Shima, Nobuyoshi Shimizu

    GENOMICS　89　(1)　124-133　2007/01

    DOI： 10.1016/j.ygeno.2006.09.003 　

    ISSN： 0888-7543

  173. Genomic organization of the sex-determining and adjacent regions of the sex chromosomes of medaka Peer-reviewed

    Mariko Kondo, Ute Hornung, Indrajit Nanda, Shuichiro Imai, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Hiroshi Hori, Michael Schmid, Nobuyoshi Shimizu, Manfred Schartl

    GENOME RESEARCH　16　(7)　815-826　2006/07

    DOI： 10.1101/gr.5016106 　

    ISSN： 1088-9051

  174. Comparative genomics of medaka and fugu

    Shimizu, N, Sasaki, T, Asakawa, S, Shimizu, A, Ishikawa, S. K, Imai, S, Murayama, Y, Himmelbauer, H, Mitani, H, Furutani-Seiki, M, Kondoh, H, Schartl, M, Nonaka, M, Takeda, H, Hori, H, Shima, A

    Comp Biochem Physiol Part D Genomics Proteomics　1　(1)　6-12　2006/03

    DOI： 10.1016/j.cbd.2005.10.008 　

    ISSN： 1878-0407

    More details Close

    A small freshwater fish medaka (Oryzias latipes) has been one of the most attractive experimental systems for research in genetics and developmental biology. We have formed an international consortium Medaka Genome Initiative (MGI) to collect and share various information and resources on medaka. The MGI has set an ambitious goal aiming at the complete sequencing of the medaka genome and as a feasibility study we have begun sequencing one particular chromosome, linkage group 22 (LG22) of approximately 22 Mb in size. Initial sequence analysis revealed unique features of the medaka genome in comparison to fugu genome.

  175. Comparative genomics of medaka and fugu Peer-reviewed

    N Shimizu, T Sasaki, S Asakawa, A Shimizu, SK Ishikawa, S Imai, Y Murayama, H Himmelbauer, H Mitani, M Furutani-Seiki, H Kondoh, M Schartl, M Nonaka, H Takeda, H Hori, A Shima

    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS　1　(1)　6-12　2006/03

    DOI： 10.1016/j.cbd.2005.10.008 　

    ISSN： 1744-117X

  176. DNA sequence and analysis of human chromosome 8

    Chad Nusbaum, Tarjei S. Mikkelsen, Michael C. Zody, Shuichi Asakawa, Stefan Taudien, Manuel Garber, Chinnappa D. Kodira, Mary G. Schueler, Atsushi Shimizu, Charles A. Whittaker, Jean L. Chang, Christina A. Cuomo, Ken Dewar, Michael G. FitzGerald, Xiaoping Yang, Nicole R. Allen, Scott Anderson, Teruyo Asakawa, Karin Blechschmidt, Toby Bloom, Mark L. Borowsky, Jonathan Butler, April Cook, Benjamin Corum, Kurt DeArellano, David DeCaprio, Kathleen T. Dooley, Lester Dorris III, Reinhard Engels, Gernot Glöckner, Nabil Hafez, Daniel S. Hagopian, Jennifer L. Hall, Sabine K. Ishikawa, David B. Jaffe, Asha Kamat, Jun Kudoh, Rüdiger Lehmann, Tashi Lokitsang, Pendexter Macdonald, John E. Major, Charles D. Matthews, Evan Mauceli, Uwe Menzel, Atanas H. Mihalev, Shinsei Minoshima, Yuji Murayama, Jerome W. Naylor, Robert Nicol, Cindy Nguyen, Sinéad B. O'Leary, Keith O'Neill, Stephen C. J. Parker, Andreas Polley, Christina K. Raymond, Kathrin Reichwald, Joseph Rodriguez, Takashi Sasaki, Markus Schilhabel, Roman Siddiqui, Cherylyn L. Smith, Tam P. Sneddon, Jessica A. Talamas, Pema Tenzin, Kerri Topham, Vijay Venkataraman, Gaiping Wen, Satoru Yamazaki, Sarah K. Young, Qiandong Zeng, Andrew R. Zimmer, Andre Rosenthal, Bruce W. Birren, Matthias Platzer, Shimizu Nobuyoshi, Eric S. Lander

    Nature　439　(7074)　331-335　2006/01/19

    Publisher: Nature Publishing Group

    DOI： 10.1038/nature04406 　

    ISSN： 1476-4687 0028-0836

  177. DNA sequence and analysis of human chromosome 8 Peer-reviewed

    C Nusbaum, TS Mikkelsen, MC Zody, S Asakawa, S Taudien, M Garber, CD Kodira, MG Schueler, A Shimizu, CA Whittaker, JL Chang, CA Cuomo, K Dewar, MG FitzGerald, XP Yang, NR Allen, S Anderson, T Asakawa, K Blechschmidt, T Bloom, ML Borowsky, J Butler, A Cook, B Corum, K DeArellano, D DeCaprio, KT Dooley, L Dorris, R Engels, G Glockner, N Hafez, DS Hagopian, JL Hall, SK Ishikawa, DB Jaffe, A Kamat, J Kudoh, R Lehmann, T Lokitsang, P Macdonald, JE Major, CD Matthews, E Mauceli, U Menzel, AH Mihalev, S Minoshima, Y Murayama, JW Naylor, R Nicol, C Nguyen, SB O&apos;Leary, K O&apos;Neill, SCJ Parker, A Polley, CK Raymond, K Reichwald, J Rodriguez, T Sasaki, M Schilhabel, R Siddiqui, CL Smith, TP Sneddon, JA Talamas, P Tenzin, K Topham, Venkataraman, V, GP Wen, S Yamazaki, SK Young, QD Zeng, AR Zimmer, A Rosenthal, BW Birren, M Platzer, N Shimizu, ES Lander

    NATURE　439　(7074)　331-335　2006/01

    DOI： 10.1038/nature04406 　

    ISSN： 0028-0836

  178. Genomic sequences encoding two types of medaka hemopexin-like protein Wap65, and their gene expression profiles in embryos Peer-reviewed

    M Nakaniwa, M Hirayama, A Shimizu, T Sasaki, S Asakawa, N Shimizu, S Watabe

    JOURNAL OF EXPERIMENTAL BIOLOGY　208　(10)　1915-1925　2005/05

    DOI： 10.1242/jeb.01570 　

    ISSN： 0022-0949

  179. Molecular cloning and characterization of gene for Golgi-localized syntaphilin-related protein on human chromosome 8q23 Peer-reviewed

    E Funakoshi, K Nakagawa, A Hamano, T Hori, A Shimizu, S Asakawa, N Shimizu, F Ito

    GENE　344　259-271　2005/01

    DOI： 10.1016/j.gene.2004.10.024 　

    ISSN： 0378-1119

  180. Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence Peer-reviewed

    S Taudien, P Galgoczy, K Huse, K Reichwald, M Schilhabel, K Szafranski, A Shimizu, S Asakawa, A Frankish, IF Loncarevic, N Shimizu, R Siddiqui, M Platzer

    BMC GENOMICS　5　92　2004/12

    DOI： 10.1186/1471-2164-5-92 　

    ISSN： 1471-2164

  181. The minimal eukaryotic ribosomal DNA units in the primitive red alga Cyanidioschyzon merolae Peer-reviewed

    S Maruyama, O Misumi, Y Ishii, S Asakawa, A Shimizu, T Sasaki, MC Matsuzaki, T Shin-I, H Nozaki, Y Kohara, N Shimizu, T Kuroiwa

    DNA RESEARCH　11　(2)　83-91　2004/04

    DOI： 10.1093/dnares/11.2.83 　

    ISSN： 1340-2838

  182. Comparative genomics of the keratin-associated protein (KAP) gene clusters in human, chimpanzee, and baboon Peer-reviewed

    K Shibuya, J Kudoh, Obayashi, I, A Shimizu, T Sasaki, S Minoshima, N Shimizu

    MAMMALIAN GENOME　15　(3)　179-192　2004/03

    DOI： 10.1007/s00335-003-2313-9 　

    ISSN： 0938-8990

  183. DMRT genes and sex determination in Medaka Peer-reviewed

    U Hornung, Nanda, I, M Kondo, A Shimizu, S Asakawa, JN Volff, C Winkler, ZH Shan, T Haaf, N Shimizu, A Shima, M Schmid, M Schartl

    CHROMOSOMES TODAY, VOL 14　14　27-+　2004

    ISSN： 0069-3944

  184. Type III Cu mutants of Myrothecium verrucaria bilirubin oxidase Peer-reviewed

    A Shimizu, T Samejima, S Hirota, S Yamaguchi, N Sakurai, T Sakurai

    JOURNAL OF BIOCHEMISTRY　133　(6)　767-772　2003/06

    DOI： 10.1093/jb/mvg098 　

    ISSN： 0021-924X

  185. Authentic and recombinant bilirubin oxidases are in different resting forms Peer-reviewed

    T Sakurai, L Zhan, T Fujita, K Kataoka, A Shimizu, T Samejima, S Yamaguchi

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　67　(5)　1157-1159　2003/05

    DOI： 10.1271/bbb.67.1157 　

    ISSN： 0916-8451

    eISSN： 1347-6947

  186. A physical map of the human genome

    JD McPherson, M Marra, L Hillier, RH Waterston, A Chinwalla, J Wallis, M Sekhon, K Wylie, ER Mardis, RK Wilson, R Fulton, TA Kucaba, C Wagner-McPherson, WB Barbazuk, SG Gregory, SJ Humphray, L French, RS Evans, G Bethel, A Whittaker, JL Holden, OT McCann, A Dunham, C Soderlund, CE Scott, DR Bentley, G Schuler, HC Chen, WH Jang, ED Green, Idol, JR, VVB Maduro, KT Montgomery, E Lee, A Miller, S Emerling, R Kucherlapati, R Gibbs, S Scherer, JH Gorrell, E Sodergren, K Clerc-Blankenburg, P Tabor, S Naylor, D Garcia, PJ de Jong, JJ Catanese, N Nowak, K Osoegawa, SZ Qin, L Rowen, A Madan, M Dors, L Hood, B Trask, C Friedman, H Massa, VG Cheung, IR Kirsch, T Reid, R Yonescu, J Weissenbach, T Bruls, R Heilig, E Branscomb, A Olsen, N Doggett, JF Cheng, T Hawkins, RM Myers, J Shang, L Ramirez, J Schmutz, O Velasquez, K Dixon, NE Stone, DR Cox, D Haussler, WJ Kent, T Furey, S Rogic, S Kennedy, S Jones, A Rosenthal, GP Wen, M Schilhabel, G Gloeckner, G Nyakatura, R Siebert, B Schlegelberger, J Korenburg, XN Chen, A Fujiyama, M Hattori, A Toyoda, T Yada, HS Park, Y Sakaki, N Shimizu, S Asakawa, K Kawasaki, T Sasaki, A Shintani, A Shimizu, K Shibuya, J Kudoh, S Minoshima, J Ramser, P Seranski, C Hoff, A Poustka, R Reinhardt, H Lehrach

    NATURE　409　(6822)　934-941　2001/02

    DOI： 10.1038/35057157 　

    ISSN： 0028-0836

    eISSN： 1476-4687

  187. Detection of measles virus genome in bronchoalveolar lavage cells in a patient with measles pneumonia Peer-reviewed

    A Shimizu, O Tanabe, C Anzai, K Uchida, H Tada, K Yoshimura

    EUROPEAN RESPIRATORY JOURNAL　15　(3)　619-622　2000/03

    DOI： 10.1034/j.1399-3003.2000.15.31.x 　

    ISSN： 0903-1936

  188. Site-directed mutagenesis of a possible type 1 copper ligand of bilirubin oxidase; a Met467Gln mutant shows stellacyanin-like properties Peer-reviewed

    A Shimizu, T Sasaki, JH Kwon, A Odaka, T Satoh, N Sakurai, T Sakurai, S Yamaguchi, T Samejima

    JOURNAL OF BIOCHEMISTRY　125　(4)　662-668　1999/04

    ISSN： 0021-924X

Show all ︎Show first 5

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    清水 厚志

    日本衛生学雑誌　77　(Suppl.)　S117-S117　2022/03

    Publisher: (一社)日本衛生学会

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    日本臨床　80　(増刊1 最新臨床脳卒中学(上))　333-338　2022/01

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    遺伝子医学　10　(2)　137-141　2020/04

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    JOURNAL OF IMMUNOLOGY　214　2025/11

    DOI： 10.1093/jimmun/vkaf283.514 　

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    日本衛生学雑誌(Web)　80　(Supplement)　2025

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    ISSN： 1347-9628

  19. 日本人マイクロアレイデータをレファレンスとして用いるエピゲノム年齢推定法の開発

    清水厚志, 清水厚志, 清水厚志, 小巻翔平, 小巻翔平, 小巻翔平, 大桃秀樹, 大桃秀樹, 大桃秀樹

    日本抗加齢医学会総会プログラム・抄録集　24th　2024

  20. DNA Methylation Study in DOHaD Theory: A Perspective from the Tohoku Medical Megabank (TMM) Project

    美辺詩織, 美辺詩織, 小巻翔平, 小巻翔平, 大桃秀樹, 大桃秀樹, 清水厚志, 清水厚志

    DOHad研究(Web)　12　(1)　2024

    ISSN： 2187-2597

  21. Association Between Glycemic Traits and POAG: A Mendelian Randomization Study

    羽入田明子, 羽入田明子, 後藤温, 後藤温, 寳澤篤, 清水厚志, 結城賢弥, 結城賢弥, 坪田一男, 坪田一男, 根岸一乃, 松尾恵太郎, 岩崎基

    日本緑内障学会抄録集　34th　2023

  22. 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

  23. 日本人集団におけるメタボロームGWAS(mGWAS)の解析手順の検討

    土岐了大, 小島駿, 小島駿, 伏木蒼太郎, 伏木蒼太郎, 原田成, 平田あや, 飯田美穂, 宮川尚子, 枝川峻, 須藤洋一, 大桃秀樹, 山崎弥生, 清水厚志, 清水厚志, 武林亨

    日本衛生学雑誌(Web)　78　(Supplement)　2023

    ISSN： 1882-6482

  24. 新生児臍帯血の網羅的エピゲノム解析による妊娠初期までの喫煙経験が次世代に及ぼす影響

    美辺詩織, 小巻翔平, 大桃秀樹, 高嶋聰, 小野加奈子, 山崎弥生, 須藤洋一, 田高周, 水野聖士, 石黒真美, 工藤久智, 小原拓, 熊田和貴, 勝岡史城, 荻島創一, 木下賢吾, 菅原準一, 栗山進一, 清水厚志, 清水厚志

    DOHad研究(Web)　11　(3)　2023

    ISSN： 2187-2597

  25. Glycemic traits and POAG: Mendelian randomization study in a Japanese population

    羽入田明子, 羽入田明子, 後藤温, 後藤温, 中杤昌弘, 若井建志, 清水厚志, 丹野高三, 木下賢吾, 寶澤篤, 伊藤秀美, 松尾恵太郎, 結城賢弥, 結城賢弥, 坪田一男, 坪田一男, 根岸一乃, 岩崎基

    日本眼科学会雑誌　127　2023

    ISSN： 0029-0203

  26. East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease

    Yunye He, Masaru Koido, Yoichi Sutoh, Mingyang Shi, Yayoi Otsuka-Yamasaki, Hans Markus Munter, Takayuki Morisaki, Akiko Nagai, Yoshinori Murakami, Chizu Tanikawa, Tsuyoshi Hachiya, Koichi Matsuda, Atsushi Shimizu, Yoichiro Kamatani

    medRxiv　2022/10/26

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2022.10.25.22281344 　

    More details Close

    Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer; GU) or duodenum (duodenal ulcer; DU). We conducted a large-scale cross-ancestry meta-analysis of PUD combining genome-wide association studies with four Japanese and two European studies (52,032 cases and 905,344 controls), and discovered 25 novel loci highly concordant across ancestries. Based on these loci, an examination of similarities and differences in genetic architecture between GU and DU demonstrated that GU shared the same risk loci as DU, although with smaller genetic effect sizes and higher polygenicity than DU, indicating higher heterogeneity of GU. H. pylori (HP)-stratified analysis found an HP-related host genetic locus, marking its role in HP-mediated PUD etiology. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD to be enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology.

  27. Expanding stroke genetics research from the MEGASTROKE Study

    八谷剛史, 八谷剛史, 清水厚志, 清水厚志

    日本臨床　80　(増刊2 最新臨床脳卒中学(下))　716-721　2022/02

    Publisher: (株)日本臨床社

    ISSN： 0047-1852

  28. ALDH2 genotype interacts the association between alcohol consumption and AST/ALT ratio among middle-aged Japanese men

    須藤洋一, 八谷剛史, 鈴木悠地, 小巻翔平, 大桃秀樹, 柿坂啓介, WANG Ting, 滝川康裕, 清水厚志, 清水厚志

    日本分子生物学会年会プログラム・要旨集(Web)　45th　2022

  29. Identification of potential DNA methylation biomarkers for detection of clear cell renal cell carcinoma in PCBD2/MTND4P12 genes.

    大桃秀樹, 大桃秀樹, 小巻翔平, 須藤洋一, 八谷剛史, 八谷剛史, 小野加奈子, 新井恵吏, 藤元博行, 吉田輝彦, 金井弥栄, 旭浩一, 佐々木真理, 清水厚志, 清水厚志

    日本分子生物学会年会プログラム・要旨集(Web)　45th　2022

  30. メンデルのランダム化法による血中脂質と大腸がんの関係の検討

    岩上 将夫, 後藤 温, 鈴木 詩織, 片桐 諒子, 羽入田 明子, 山地 太樹, 澤田 典絵, 中杤 昌弘, 若井 建志, 須藤 洋一, 清水 厚志, 丹野 高三, 木下 賢吾, 寳澤 篤, 伊藤 秀美, 松尾 恵太郎, 岩崎 基, J-CGEグループ

    Journal of Epidemiology　32　(Suppl.1)　155-155　2022/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  31. Genetic factors

    八谷剛史, 八谷剛史, 清水厚志, 清水厚志

    日本臨床　80　(増刊1 最新臨床脳卒中学(上))　333-338　2022/01

    Publisher: (株)日本臨床社

    ISSN： 0047-1852

  32. 【精神疾患の網羅的ゲノム解析〜課題と展望】東北メディカル・メガバンク計画における大規模ゲノム・オミックス解析と疾患発症リスク予測

    梅影 創, 清水 厚志

    日本生物学的精神医学会誌　32　(2)　68-74　2021/06

    Publisher: 日本生物学的精神医学会

    ISSN： 2186-6619

    eISSN： 2186-6465

  33. Cancer resistance in naked mole-rats via a dampened inflammatory response

    藤岡周助, 藤岡周助, 岡香織, 河村佳見, 河村佳見, 菰原義弘, 中條岳志, 山村祐紀, 大岩祐基, 須藤洋一, 小巻翔平, 大豆生田夏子, 櫻井智子, 清水厚志, 坊農秀雅, 富澤一仁, 山本拓也, 山田泰広, 押海裕之, 三浦恭子, 三浦恭子

    日本薬学会年会要旨集(Web)　141st　29V08-am11S　2021/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  34. ヒトゲノム解読の歴史とゲノム情報の衛生学への応用

    清水 厚志

    日本衛生学雑誌　76　(Suppl.)　S86-S86　2021/03

    Publisher: (一社)日本衛生学会

    ISSN： 0021-5082

    eISSN： 1882-6482

  35. ポリジェニックリスクスコアのがん予防や治療への実装と課題

    清水厚志

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

  36. Large-scale genomic and omics analysis and risk prediction of disease incidence in Tohoku Medical Megabank Project

    梅影創, 清水厚志

    日本生物学的精神医学会誌(Web)　32　(2)　99-99　2021

    Publisher: 日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会

    ISSN： 2186-6465

  37. 大規模ゲノムコホート連携と遺伝情報を活用した疾患発症リスク予測モデルによる個別化予防の実現

    清水厚志

    日本疫学会学術総会講演集(Web)　31st　(Suppl.1)　55-55　2021/01

    Publisher: (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  38. 大規模ゲノムコホート研究における疾患発症リスク予測

    清水 厚志

    臨床病理　68　(補冊)　011-011　2020/10

    Publisher: (一社)日本臨床検査医学会

    ISSN： 0047-1860

  39. 岩手県における東日本大震災後の住居形態による社会的孤立の状況

    事崎由佳, 丹野高三, 大塚耕太郎, 佐々木亮平, 高梨信之, 三上貴浩, 清水厚志, 坂田清美

    日本公衆衛生学会総会抄録集　79th　2020

    ISSN： 1347-8060

  40. 岩手県における東北メディカル・メガバンク計画地域住民コホート調査詳細二次調査受診者と未受診者の特徴

    事崎由佳, 丹野高三, 佐々木亮平, 高梨信之, 三上貴浩, 大塚耕太郎, 旭浩一, 那須崇人, 佐藤衛, 大桃秀樹, 清水厚志, 石垣泰, 坂田清美, 佐々木真理

    日本疫学会学術総会講演集(Web)　30th　2020

  41. The Longitudinal Changes in Cardiovascular Biomarkers in Community Dwellers: The Tohoku Medical Megabank Project

    Yuka Kotozaki, Kozo Tanno, Koichi Asahi, Takahito Nasu, Hideki Ohmomo, Ryo Otomo, Fumitaka Tanaka, Atsushi Shimizu, Kiyomi Sakata, Makoto Sasaki, Mamoru Satoh

    CIRCULATION　140　2019/11

    ISSN： 0009-7322

    eISSN： 1524-4539

  42. 東日本大震災後の仕事の変化によるメンタルヘルスの経年変化 TMM CommCohort Study

    高梨 信之, 丹野 高三, 佐々木 亮平, 事崎 由佳, 三上 貴浩, 寳澤 篤, 坪田 恵, 田鎖 愛理, 大塚 耕太郎, 清水 厚志, 坂田 清美

    日本公衆衛生学会総会抄録集　78回　241-241　2019/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  43. 東日本大震災後の岩手県における腹囲と内臓脂肪面積の経時変化 地域住民コホート調査

    事崎 由佳, 丹野 高三, 清水 厚志, 坂田 清美, 佐藤 衛

    日本公衆衛生学会総会抄録集　78回　338-338　2019/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  44. 抑うつ症状の指標と関連するDNAメチル化マーカーのキャプチャ法による探索

    小野 加奈子, 大桃 秀樹, 福本 健太郎, 小巻 翔平, 事崎 由佳, 八谷 剛史, 大友 亮, 篠崎 夏子, 志波 優, 古川 亮平, 須藤 洋一, 大塚 耕太郎, 佐々木 真理, 清水 厚志

    日本遺伝カウンセリング学会誌　40　(2)　162-162　2019/07

    Publisher: (一社)日本遺伝カウンセリング学会

    ISSN： 1347-9628

  45. DNAメチル化多様性に基づく効率的なエピゲノムマーカー探索手法の確立

    清水 厚志, 八谷 剛史, 大友 亮, 大桃 秀樹, 須藤 洋一, 小巻 翔平, 志波 優, 古川 亮平, 篠崎 夏子, 小野 加奈子, 佐々木 真理

    日本遺伝カウンセリング学会誌　40　(2)　87-87　2019/07

    Publisher: 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  46. メガゲノム時代の糖尿病学 バイオバンク・ゲノムコホート連携による疾患発症リスク予測モデルの構築

    清水 厚志

    糖尿病　62　(Suppl.1)　S-62　2019/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  47. 糖尿病群と非糖尿病群におけるPW=Vに関連する因子の違いの検討

    武部 典子, 丹野 高三, 大桃 秀樹, 佐藤 衛, 清水 厚志, 坂田 清美, 石垣 泰, 佐々木 真理

    日本内分泌学会雑誌　95　(1)　396-396　2019/04

    Publisher: (一社)日本内分泌学会

    ISSN： 0029-0661

  48. メガゲノム時代の糖尿病学 バイオバンク・ゲノムコホート連携による疾患発症リスク予測モデルの構築

    清水 厚志

    糖尿病　62　(Suppl.1)　S-62　2019/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

  49. 東日本大震災後の岩手県における社会的孤立の変化とその関連要因―地域住民コホート調査―

    事崎由佳, 丹野高三, 佐々木亮平, 高梨信之, 三上貴浩, 寳澤篤, 栗山進一, 辻一郎, 大塚耕太郎, 佐藤衛, 大桃秀樹, 清水厚志, 人見次郎, 坂田清美, 佐々木真理

    日本疫学会学術総会講演集(Web)　29th　122 (WEB ONLY)　2019/01/30

  50. 日本人のストレス対処行動に関するGWAS解析:J‐MICC Study

    島ノ江千里, 八谷剛史, 原めぐみ, 須藤洋一, 西田裕一郎, 清水厚志, 田中恵太郎

    日本疫学会学術総会講演集(Web)　29th　92 (WEB ONLY)　2019/01/30

  51. 多因子疾患の関連解析を目的とした網羅的DNAメチル化解析法の開発

    大桃秀樹, 小野加奈子, 須藤洋一, 小巻翔平, 大友亮, 八谷剛史, 佐々木真理, 清水厚志

    日本分子生物学会年会プログラム・要旨集(Web)　42nd　2019

  52. 東日本大震災後の社会的孤立と抑うつ症状との関連 TMM CommCohort Study

    事崎 由佳, 丹野 高三, 佐々木 亮平, 高梨 信之, 三上 貴浩, 寳澤 篤, 栗山 進一, 辻 一郎, 高橋 宗康, 清水 厚志, 人見 次郎, 坂田 清美

    日本公衆衛生学会総会抄録集　77回　463-463　2018/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  53. 東日本大震災後の心理的苦痛有病割合の推移 地域住民コホート調査

    丹野 高三, 佐々木 亮平, 高梨 信之, 事崎 由佳, 三上 貴浩, 高橋 宗康, 寳澤 篤, 栗山 進一, 辻 一郎, 清水 厚志, 人見 次郎, 坂田 清美

    日本公衆衛生学会総会抄録集　77回　506-506　2018/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  54. 糖尿病と非糖尿病における上腕 足首脈波伝播速度(baPWV)に関連する因子の解析

    武部 典子, 半谷 真理, 丹野 高三, 大桃 秀樹, 佐藤 衛, 清水 厚志, 坂田 清美, 石垣 泰, 佐々木 真理

    糖尿病　61　(Suppl.1)　S-258　2018/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  55. グリコアルブミン/HbA1c比に影響を及ぼす因子の検討

    半谷 真理, 武部 典子, 丹野 高三, 大桃 秀樹, 佐藤 衛, 清水 厚志, 坂田 清美, 石垣 泰, 佐々木 真理

    糖尿病　61　(Suppl.1)　S-433　2018/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  56. 日本人成人の余暇時間の運動に関するGWAS研究:J‐MICC Study

    原めぐみ, 八谷剛史, 西田裕一郎, 島ノ江千里, 清水厚志, 田中恵太郎

    日本疫学会学術総会講演集(Web)　28th　133 (WEB ONLY)　2018/02/01

  57. 問診票入力から国際基準の医療用家系図を自動作成する家系情報収集ツールの開発

    徳富 智明, 福島 明宗, 山本 佳世乃, 中山 文予, 勝部 暢介, 清水 厚志, 佐々木 真理

    日本遺伝カウンセリング学会誌　38　(4)　117-125　2018/01

    Publisher: 日本遺伝カウンセリング学会

    ISSN： 1347-9628

    More details Close

    問診票に入力するだけで自動的に医療用家系図が作成できるソフトウェア「f-tree(エフツリー)」最新版の使用方法を解説し、現在利用が可能な海外の家族歴ツールについても紹介した。f-treeは描画を目的とした従来のソフトとは異なり、問診票をベースとした新しい自動家系図作成ソフトである。f-treeの特徴は、問診票ベースのため専門的な知識や作図スキルを必要としないこと、医療用家系図の国際的ルールを100%準拠していること、データとして一度に大量の家系図を含む家系情報として取扱いができることである。f-treeは、いわて東北メディカル・メガバンク機構のホームページから無料でダウンロードできる。海外の家族歴ツールには、My Family Health Portrait、Family History Tool、ZibdyHealth、Family History Questionnaire、MeTree、Probandなどがある。

  58. 【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

  59. 【多段階発がん過程におけるエピゲノム異常】 がんの全エピゲノム関連解析(EWAS)

    大友 亮, 篠崎 夏子, 清水 厚志

    細胞　49　(8)　373-376　2017/07

    Publisher: (株)ニュー・サイエンス社

    ISSN： 1346-7557

  60. ゲノムコホート研究における家系情報の収集を目的とした折りたたみ式問診票の開発

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    日本遺伝カウンセリング学会誌　38　(2)　96-96　2017/05

    Publisher: 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  61. 一般集団への家族性高コレステロール血症(FH)の遺伝情報回付パイロット研究における事前アンケートについて

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    日本遺伝カウンセリング学会誌　38　(2)　97-97　2017/05

    Publisher: 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  62. 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

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    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

  63. 東日本大震災被災地住民の健康知識に関連する要因の検討

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    日本公衆衛生学会総会抄録集　75回　581-581　2016/10

    Publisher: 日本公衆衛生学会

    ISSN： 1347-8060

  64. 【エピゲノム研究 修飾の全体像の理解から先制・個別化医療へ 解析手法の標準化、細胞間・個人間の多様性の解明、疾患エピゲノムを標的とした診断・創薬】 (第2章)形質の多様性をつくるエピゲノム 全エピゲノム関連解析(EWAS)

    古川 亮平, 八谷 剛史, 清水 厚志

    実験医学　34　(10)　1574-1580　2016/06

    Publisher: (株)羊土社

    ISSN： 0288-5514

  65. 【ビッグデータから読み解く生命現象】 IMMオミックスリファレンスパネルの取り組み

    古川 亮平, 清水 厚志

    生化学　88　(1)　36-43　2016/02

    Publisher: (公社)日本生化学会

    DOI： 10.14952/SEIKAGAKU.2016.880036 　

    ISSN： 0037-1017

  66. 診療情報提供書における自動家系図作成ソフト活用の試み

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    日本小児遺伝学会学術集会プログラム・抄録集　39th　2016

  67. 稀少疾患の分子病態メカニズム エンドソーム系の平衡の破綻 機能亢進型SAMD9変異によるMIRAGE症候群

    鳴海 覚志, 天野 直子, 石井 智弘, 勝又 規行, 福澤 龍二, 芝田 晋介, 岡野 栄之, 清水 厚志, 三宅 紀子, 松本 直通, 長谷川 奉延

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[1W5-p　2015/12

    Publisher: (公社)日本生化学会

  68. MIRAGE症候群:機能亢進型SAMD9変異を原因とする新規症候群の発見

    鳴海覚志, 天野直子, 石井智弘, 勝又規行, 福澤龍二, 清水厚志, 三宅紀子, 松本直通, 長谷川奉延

    日本内分泌学会雑誌　91　(3)　792　2015/10/20

    ISSN： 0029-0661

  69. 遺伝学的知識についての講習会受講前後の遺伝の知識と遺伝情報回付に対する需要の変化

    YAMAMOTO KAYONO, YAMAMOTO KAYONO, AIZAWA FUMIE, NAGAMI FUJI, KAWAME YUTAKA, SOBUE KENJI, FUKUSHIMA AKIMUNE, FUKUSHIMA AKIMUNE, SHIMIZU ATSUSHI

    日本遺伝カウンセリング学会誌　36　(2)　69-atsushi_ngs　2015/05

    ISSN： 1347-9628

  70. ゲノムコホート研究への適用を目指した新たな自動家系図作成ソフトの開発

    FUKUSHIMA AKIMUNE, FUKUSHIMA AKIMUNE, KOBAYASHI YUMIKO, YAMAMOTO KAYONO, YAMAMOTO KAYONO, HACHIYA TSUYOSHI, SHIMIZU ATSUSHI

    日本遺伝カウンセリング学会誌　36　(2)　85　2015/05

    ISSN： 1347-9628

  71. MIRAGE症候群:機能亢進型SAMD9変異を原因とする新規症候群の発見

    鳴海覚志, 天野直子, 石井智弘, 勝又規行, 福澤龍二, 芝田晋介, 岡野栄之, 清水厚志, 三宅紀子, 松本直通, 長谷川奉延

    日本人類遺伝学会大会プログラム・抄録集　60th　221　2015

  72. MIRAGE症候群:副腎低形成を伴う新規症候群の疾患概念の確立と責任遺伝子の同定

    天野直子, 天野直子, 鳴海覚志, 石井智弘, 勝又規行, 福澤龍二, 清水厚志, 三宅紀子, 松本直通, 長谷川奉延

    日本小児内分泌学会学術集会プログラム・抄録集　49th　266　2015

  73. Epigenome-wide evaluation of short-term DNA methylation stability in monocytes.

    R. Furukawa, T. Hachiya, H. Ohmomo, Y. Shiwa, K. Ono, S. Suzuki, M. Satoh, J. Hitomi, K. Sobue, A. Shimizu

    MOLECULAR BIOLOGY OF THE CELL　25　2014/12

    ISSN： 1059-1524

    eISSN： 1939-4586

  74. 次世代シークエンサーと解析パネルを用いたNF1遺伝子診断法の構築

    丸岡亮, 武内俊樹, 清水厚志, 鳥居千春, 三須久美子, 日笠幸一郎, 松田文彦, 太田有史, 谷戸克己, 倉持朗, 有馬好美, 大塚藤男, 吉田雄一, 森山啓司, 小崎里華, 新村眞人, 佐谷秀行, 小崎健次郎

    日本レックリングハウゼン病学会学術大会プログラム・抄録集　6th　46-46　2014/10/20

    Publisher: 日本レックリングハウゼン病学会

  75. 次世代シークエンサーを用いたNF1遺伝子診断法の確立

    丸岡亮, 武内俊樹, 清水厚志, 鳥居千春, 三須久美子, 日笠幸一郎, 松田文彦, 太田有史, 谷戸克己, 倉持朗, 有馬好美, 大塚藤男, 吉田雄一, 森山啓司, 新村眞人, 佐谷秀行, 小崎健次郎

    日本レックリングハウゼン病学会雑誌　5　(1)　19-22　2014/04/01

    Publisher: 日本レックリングハウゼン病学会

    ISSN： 2185-5773

  76. 分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 遺伝性疾患の多層オミックス統合解析の基盤構築

    SHIMIZU ATSUSHI, HACHIYA TAKESHI, OMOMO HIDEKI, SHIWA YU, FURUKAWA RYOHEI

    分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 平成25年度 総括・分担研究報告書　34-36　2014

  77. 分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 次世代シーケンサーによる解析法の最適化と標準化に関する研究

    KUDO JUN, KOSAKI KENJIRO, SHIMIZU ATSUSHI, TORII CHIHARU

    分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 平成25年度 総括・分担研究報告書　30-33　2014

  78. 癌化耐性ハダカデバネズミiPS細胞はARFの種特異的発現様式により奇形腫形成能を獲得しない

    MIYAWAKI SHINGO, KAWAMURA YOSHIMI, SHIMIZU ATSUSHI, ONISHI NOBUYUKI, SUZUKI SADAFUMI, HACHIYA TSUYOSHI, MATSUZAKI YUMI, SAYA HIDEYUKI, OKANO HIDEYUKI, MIURA KYOKO

    日本分子生物学会年会プログラム・要旨集(Web)　37th　WEB ONLY 2P-0794　2014

  79. 遠隔地から輸送されたヒト末梢血単核球を用いたトランスクリプトーム解析のための新規プロトコールの確立

    OMOMO HIDEKI, HACHIYA TSUYOSHI, SHIWA YU, FURUKAWA RYOHEI, ONO KANAKO, ITO SHIGEKI, ISHIDA YOJI, SATO MAMORU, HITOMI JIRO, SOBUE KENJI, SHIMIZU ATSUSHI

    日本分子生物学会年会プログラム・要旨集(Web)　37th　WEB ONLY 2P-0979　2014

  80. 大規模バイオバンクにおけるヒト末梢血細胞のDNAメチル化安定性の評価

    SHIWA YU, FURUKAWA RYOHEI, OMOMO HIDEKI, ONO KANAKO, SATO MAMORU, HITOMI JIRO, SOBUE KENJI, HACHIYA TSUYOSHI, SHIMIZU ATSUSHI

    日本分子生物学会年会プログラム・要旨集(Web)　37th　WEB ONLY 1P-0029　2014

  81. いわて東北メディカル・メガバンク機構の目指す先制医療に向けた試み

    SHIMIZU ATSUSHI, HACHIYA TSUYOSHI, TANNO KOZO, FUKUSHIMA AKIMUNE, SHIWA YU, OMOMO HIDEKI, FURUKAWA RYOHEI, YAMAMOTO KAYONO, ONO KANAKO, SATO MAMORU, HITOMI JIRO, SOBUE KENJI

    日本遺伝子診療学会大会プログラム・抄録集　21st　359　2014

  82. 新規自然発症皮膚炎原因遺伝子mattedの同定

    佐々木貴史, 塩濱愛子, 久保亮治, 川崎洋, 山本明美, 山田健人, 蜂矢隆久, 清水厚志, 岡野栄之, 工藤純, 天谷雅行

    日本臨床免疫学会会誌　36　(5)　331-387a　2013/10/31

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.36.387a 　

    ISSN： 0911-4300

  83. ダブルハプロイド個体を活用したトラフグゲノムアセンブリ高精度化の検討

    張虹, 陳盈光, 木下滋晴, 浅川修一, 鈴木穣, 清水厚志, 岡野栄之, 工藤純, 斎藤和敬, 渡部終五

    日本水産学会大会講演要旨集　2013　48　2013/09/19

  84. 次世代シーケンサーを用いた脊髄損傷に対するヒトiPS細胞由来神経幹細胞移植の安全性の検討

    海苔聡, 西村空也, 小林喜臣, 佐々木貴史, 清水厚志, 工藤純, 山中伸弥, 岡野栄之, 戸山芳昭, 中村雅也

    日本整形外科学会雑誌　87　(8)　S1561　2013/08/30

    ISSN： 0021-5325

  85. マーモセット損傷脊髄内の微小環境解析と細胞移植の至適時期の検討

    西村空也, 岩井宏樹, 小林喜臣, 吉田賢司, 芝田晋介, 海老瀬速雄, 佐々木貴史, 清水厚志, 工藤純, 岡野栄之, 戸山芳昭, 中村雅也

    日本整形外科学会雑誌　87　(8)　S1427　2013/08/30

    ISSN： 0021-5325

  86. 老化耐性・がん化耐性ハダカデバネズミの分子生物学的研究の展開

    三浦恭子, 宮脇慎吾, 清水厚志, 八谷剛史, 河村佳見, 土屋喜洋, 本間小百合, 成田年, 榊原康文, 岡野栄之

    日本動物学会大会予稿集　84th　63　2013/08/12

  87. 老化耐性・がん化耐性ハダカデバネズミの分子生物学的研究の展開

    三浦恭子, 宮脇慎吾, 清水厚志, 八谷剛史, 土屋喜洋, 本間小百合, 成田年, 榊原康文, 岡野栄之

    日本実験動物学会総会講演要旨集　60th　127　2013/04/26

  88. 次世代シークエンサーの臨床応用:NF1を対象としたバリデーション研究

    丸岡亮, 鳥居千春, 清水厚志, 森山啓司, 小崎健次郎

    日本小児遺伝学会学術集会プログラム・抄録集　36th　26　2013/04/18

  89. 脊髄損傷に対するiPS細胞由来神経幹細胞移植の安全性の確保に向けて

    海苔聡, 西村空也, 小林喜臣, 佐々木貴史, 清水厚志, 工藤純, 山中伸弥, 岡野栄之, 戸山芳昭, 中村雅也

    J Spine Res　4　(3)　205　2013/03/25

    ISSN： 1884-7137

  90. マーモセット損傷脊髄内の微小環境の網羅的解析

    西村空也, 岩井宏樹, 小林喜臣, 吉田賢司, 佐々木貴史, 清水厚志, 工藤純, 岡野栄之, 戸山芳昭, 中村雅也

    J Spine Res　4　(3)　271　2013/03/25

    ISSN： 1884-7137

  91. 老化耐性・がん化耐性ハダカデバネズミの分子生物学的研究の展開

    三浦恭子, 宮脇慎吾, 清水厚志, 八谷剛史, 土屋喜洋, 本間小百合, 新井奈月, 成田年, 榊原康文, 岡野栄之

    日本獣医学会学術集会講演要旨集　155th　171　2013/03/04

    ISSN： 1347-8621

  92. マーモセット損傷脊髄内の微小環境解析と細胞移植の至適時期の検討

    西村空也, 岩井宏樹, 小林喜臣, 吉田賢司, 海老瀬速雄, 佐々木貴史, 清水厚志, 工藤純, 戸山芳昭, 岡野栄之, 中村雅也

    再生医療　12　187　2013/02/28

    ISSN： 1347-7919

  93. W1-6  新規自然発症皮膚炎原因遺伝子mattedの同定

    佐々木 貴史, 塩濱 愛子, 久保 亮治, 川崎 洋, 山本 明美, 山田 健人, 蜂矢 隆久, 清水 厚志, 岡野 栄之, 工藤 純, 天谷 雅行

    日本臨床免疫学会会誌　36　(5)　331b-331b　2013

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.36.331b 　

    ISSN： 0911-4300

    More details Close

    皮膚バリア主要構成成分フィラグリン（FLG）の遺伝子変異は，アトピー性皮膚炎（AD）の発症因子であることが報告された．Flaky tailマウスは体毛異常を示すma変異マウスコロニーから自然発生したマウスで，皮膚炎を自然発症すること，Flg変異（Flgft）を有することからADモデルとして広く使われている．我々が作製したFlg KOは皮膚炎を自然発症しないことから，Flgftとmaを分離した結果，ma/maマウスだけが皮膚炎を自然発症した．ma責任領域を次世代シーケンサーで解読した結果，Matted遺伝子にナンセンス変異を同定した．そのMatted遺伝子をma/maマウスに発現させたところ皮膚炎を発症しないことから，Matted遺伝子が原因遺伝子であると同定した．Matted mRNAは皮膚に発現し，Mattedタンパクは表皮顆粒層細胞質内に網目状に局在した．Mattedタンパクの細胞内局在は細胞内小胞輸送に関与するTrans-Golgi networkのマーカータンパクと最も一致した．ma/maマウスでは小胞輸送により細胞外分泌される角質層形成タンパク群が減少し，角層剥離異常を認めた．以上の結果から，ma/maマウスの自然発症皮膚炎はMatted遺伝子の欠損が原因であり，この結果は皮膚バリア異常と皮膚炎発症のメカニズムを解明する重要な手がかりとなると考えられる．

  94. P4-03  新規自然発症皮膚炎原因遺伝子mattedの同定

    佐々木 貴史, 塩濱 愛子, 久保 亮治, 川崎 洋, 山本 明美, 山田 健人, 蜂矢 隆久, 清水 厚志, 岡野 栄之, 工藤 純, 天谷 雅行

    日本臨床免疫学会会誌　36　(5)　387a-387a　2013

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.36.387a 　

    ISSN： 0911-4300

    More details Close

    「ワークショップ選出演題「ワークショップW1-6」抄録は331ページ参照」

  95. 分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 次世代シークエンサーによる先天異常症患者ゲノム変異探索システムの改良

    清水厚志

    分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 平成24年度 総括・分担研究報告書　23-26　2013

  96. VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立 VATER症候群の次世代シーケンサーによる遺伝子解析に関する研究

    工藤純, 清水厚志, 鳥居千春, 小崎健次郎

    VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立 平成24年度 総括・分担研究報告書　24-25　2013

  97. VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立 VATER症候群の次世代シーケンサーによる遺伝子解析に関する研究

    工藤純, 清水厚志, 鳥居千春, 小崎健次郎

    VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立 平成23-24年度 総合研究報告書　39-40　2013

  98. 分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 次世代シーケンサーによる解析に関する研究

    工藤純, 清水厚志, 鳥居千春, 小崎健次郎

    分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 平成24年度 総括・分担研究報告書　21-22　2013

  99. がん化耐性齧歯類ハダカデバネズミiPS細胞はArfの発現抑制からの防御により腫瘍形成能をもたない

    宮脇慎吾, 清水厚志, 八谷剛史, 土屋喜洋, 成田年, 榊原康文, 岡野栄之, 三浦恭子

    日本分子生物学会年会プログラム・要旨集(Web)　36th　WEB ONLY 1P-0941　2013

  100. 老化耐性・がん化耐性齧歯類ハダカデバネズミの分子生物学的研究の展開

    三浦恭子, 宮脇慎吾, 河村佳見, 清水厚志, 八谷剛史, 関布美子, 疋島啓吾, 土屋喜洋, 本間小百合, 成田年, 榊原康文, 岡野栄之

    日本分子生物学会年会プログラム・要旨集(Web)　36th　WEB ONLY 1PW3-3　2013

  101. 日本人メチローム・トランスクリプトームリファレンスパネル構築のフィージビリティ研究

    清水厚志

    日本遺伝子診療学会大会プログラム・抄録集　20th　80　2013

  102. 次世代シークエンサーによる発現変動遺伝子の同定

    清水厚志

    月刊メディカル・サイエンス・ダイジェスト　38　(13)　587-588　2012/11/25

    ISSN： 1347-4340

  103. Versican Secretion from Endocardium is Required for Chamber Formation via The Recruitment of Cardiac Progenitors

    Sung-Han Yoon, Yuta Higashikuse, Toshimi Kageyama, Mayumi Oda, Ruri Kaneda, Motoaki Sano, Shinsuke Yuasa, Misato Fujita, Atsushi Kawakami, Atsushi Shimizu, Sonoko Hatano, Hideto Watanabe, Akira Kudo, Shinji Makino, Keiichi Fukuda

    CIRCULATION　126　(21)　2012/11

    ISSN： 0009-7322

    eISSN： 1524-4539

  104. マーモセット損傷脊髄内の微小環境の網羅的解析

    西村空也, 岩井宏樹, 小林喜臣, 吉田賢司, 芝田晋介, 佐々木貴史, 清水厚志, 工藤純, 戸山芳昭, 岡野栄之, 中村雅也

    日本整形外科学会雑誌　86　(8)　S1296　2012/08/25

    ISSN： 0021-5325

  105. 次世代シーケンサーを用いた先天奇形症候群の網羅的診断

    鳥居千春, 丸岡亮, 清水厚志, 小崎里華, 小崎健次郎

    日本先天異常学会学術集会プログラム・抄録集　52nd　76　2012/07

  106. Hirschsprung病および類縁疾患に対する病態解明と再生治療に関する研究

    下島直樹, 森川康英, 森昌玄, 藤村匠, 芝田晋介, 堀田亮, 西川竜平, 清水厚志, 古家育子, 塩濱愛子, 工藤純, 小崎健次郎, 中村雅也, 新部邦透, 森川暁, 馬渕洋, 松崎有未, 岡野ジェームス洋尚, 岡野栄之, 黒田達夫

    日本小児外科学会雑誌　48　(3)　472-472　2012/05/01

    Publisher: (一社)日本小児外科学会

    ISSN： 0288-609X

    eISSN： 2187-4247

  107. CHARGE症候群の成人期の病像の解明と遺伝子診断の臨床応用・iPS細胞の確立に関する研究 CHARGE症候群の次世代シーケンサーによる遺伝子解析

    工藤純, 清水厚志, 鳥居千春, 小崎健次郎

    CHARGE症候群の成人期の病像の解明と遺伝子診断の臨床応用・iPS細胞の確立に関する研究 平成23年度 総括・分担研究報告書　27-30　2012

  108. VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立 VATER症候群の次世代シーケンサーによる遺伝子解析

    工藤純, 清水厚志, 鳥居千春, 小崎健次郎

    VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立 平成23年度 総括・分担研究報告書　34-35　2012

  109. CHARGE症候群の成人期の病像の解明と遺伝子診断の臨床応用・iPS細胞の確立に関する研究 CHARGE症候群の次世代シーケンサーによる遺伝子解析

    工藤純, 清水厚志, 鳥居千春, 小崎健次郎

    CHARGE症候群の成人期の病像の解明と遺伝子診断の臨床応用・iPS細胞の確立に関する研究 平成22-23年度 総合研究報告書　38-42　2012

  110. 分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 次世代シーケンサーによる解析に関する研究

    工藤純, 清水厚志, 鳥居千春, 小崎健次郎

    分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 平成23年度 総括・分担研究報告書　23-24　2012

  111. 超長寿ハダカデバネズミにおけるiPS細胞の樹立

    宮脇慎吾, 清水厚志, 八谷剛史, 土屋喜洋, 新井奈月, 成田年, 榊原康文, 岡野栄之, 三浦恭子

    日本分子生物学会年会プログラム・要旨集(Web)　35th　WEB ONLY 3P-0425　2012

  112. 肥厚性皮膚骨膜症における遺伝子診断と生化学的検査を踏まえた新しい病型分類の提言と既存治療法の再評価に関する研究 次世代シーケンサーを用いた肥厚性皮膚骨膜症の原因遺伝子の探索

    工藤純, 佐々木貴史, 新関寛徳, 清水厚志, 塩濱愛子, 椛島健治, 大塚篤司, 石河晃, 関敦仁

    肥厚性皮膚骨膜症における遺伝子診断と生化学的検査を踏まえた新しい病型分類の提言と既存治療法の再評価に関する研究 平成22-23年度 総合研究報告書　62-66　2012

  113. 分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 次世代シークエンサーによる変異探索システムの構築

    清水厚志

    分野横断型全国コンソーシアムによる先天異常症の遺伝要因の解明と遺伝子診断ネットワークの形成 平成23年度 総括・分担研究報告書　25-26　2012

  114. 老化耐性・がん化耐性ハダカデバネズミの分子生物学的研究の展開

    三浦恭子, 宮脇慎吾, 清水厚志, 八谷剛史, 土屋喜洋, 新井奈月, 成田年, 榊原康文, 岡野栄之

    日本分子生物学会年会プログラム・要旨集(Web)　35th　WEB ONLY 3W1I-8　2012

  115. 次世代シーケンサーを用いたエキソーム解析による肥厚性皮膚骨膜症原因遺伝子SLCO2A1の同定

    佐々木貴史, 新関寛徳, 清水厚志, 塩濱愛子, 開山麻美, 奥山虎之, 関敦仁, 椛島健治, 大塚篤司, 石河晃, 宮川俊一, 天谷雅行, 岡野栄之, 末松誠, 工藤純

    日本人類遺伝学会大会プログラム・抄録集　57th　159　2012

  116. 肥厚性皮膚骨膜症における遺伝子診断と生化学的検査を踏まえた新しい病型分類の提言と既存治療法の再評価に関する研究 次世代シーケンサーを用いた肥厚性皮膚骨膜症の原因遺伝子の探索

    工藤純, 佐々木貴史, 新関寛徳, 清水厚志, 塩濱愛子, 椛島健治, 大塚篤司, 石河晃, 関敦仁

    肥厚性皮膚骨膜症における遺伝子診断と生化学的検査を踏まえた新しい病型分類の提言と既存治療法の再評価に関する研究 平成23年度総括・分担研究報告書　43-47　2012

  117. メダカSox5は色素細胞の運命決定に関与する

    長尾勇佑, 足立朋子, 清水厚志, 関良子, 井上慎子, 亀井保博, 原育代, 木村哲晃, 谷口善仁, 成瀬清, KELSH Robert, 若松佑子, 日比正彦, 橋本寿史

    日本分子生物学会年会プログラム・要旨集(Web)　35th　WEB ONLY 3P-0549　2012

  118. トランスジェニックメダカにおける2種の蛍光レポータータンパク遺伝子の組織特異的発現はインシュレーターによって厳格に制御できる

    清水厚志, 清水信義

    日本分子生物学会年会プログラム・要旨集(Web)　35th　WEB ONLY 1P-0229　2012

  119. カスタムターゲットリシーケンスによる難聴関連遺伝子の変異探索

    鈴木直大, 務台英樹, 鳥居千春, 清水厚志, 宮冬樹, 難波一徳, 工藤純, 小崎健次郎, 松永達雄

    日本人類遺伝学会大会プログラム・抄録集　57th　164　2012

  120. Dual promoter expression system with insulator ensures a stringent tissue-specific regulation of two reporter genes in the transgenic fish.

    SHIMIZU ATSUSHI

    Transgenic Research　2012

    DOI： 10.1007/s11248-012-9653-8 　

  121. 分裂期チェックポイント分子BUBR1は脊椎動物における繊毛形成を制御する

    宮本達雄, PORAZINSKI Sean, WANG Huijia, 清水厚志, 梶井正, 菊池章, 古谷(清水)誠, 松浦伸也

    日本放射線影響学会大会講演要旨集　54th　96　2011/11/01

    DOI： 10.11513/jrrsabst.2011.0.93.0 　

    ISSN： 1347-8680

  122. C-14 霊長類におけるLCRの構造解析とCore Dupliconの同定

    清水 厚志

    霊長類研究所年報　41　36[127]-36[127]　2011/10/21

    Publisher: 京都大学霊長類研究所

    ISSN： 0286-4568

  123. 14.ヒルシュスプルング病類縁疾患(hypoganglionosis)に対する次世代シーケンサーを用いた遺伝子解析(一般演題,第41回日本小児消化管機能研究会)

    下島 直樹, 清水 厚志, 古家 育子, 芝田 晋介, 岡野 ジェイムス洋尚, 松尾 光一, 工藤 純, 岡野 栄之, 森川 康英

    日本小児外科学会雑誌　47　(6)　984-984　2011/10/20

    Publisher: 特定非営利活動法人日本小児外科学会

    DOI： 10.11164/jjsps.47.6_984_2 　

    ISSN： 0288-609X

  124. ヒルシュスプルング病類縁疾患(hypoganglionsis)に対する次世代シーケンサーを用いた遺伝子解析

    下島直樹, 清水厚志, 古家育子, 芝田晋介, 岡野ジェイムス洋尚, 松尾光一, 工藤純, 岡野栄之, 森川康英

    日本小児外科学会雑誌　47　(6)　984-984　2011/10/20

    Publisher: 特定非営利活動法人 日本小児外科学会

    DOI： 10.11164/jjsps.47.6_984_2 　

    ISSN： 0288-609X

  125. 高温耐性ニジマスの全ゲノムシーケンシング

    浅川修一, 陳インコン, 木下滋晴, 大島健志朗, 服部正平, 鈴木穣, 清水厚志, 岡野栄之, 工藤純, 武藤光司, 矢田崇, 内田和夫, 稲野俊直, 田牧幸一, 毛良明夫, 渡部終五

    日本水産学会大会講演要旨集　2011　41　2011/09/28

  126. RNAの解析〈RNA解析の新技術〉次世代シークエンサーによるトランスクリプトーム解析

    清水厚志

    臨床検査　55　(9)　841-846　2011/09/15

    Publisher: 医学書院

    DOI： 10.11477/mf.1542102720 　

    ISSN： 0485-1420

  127. Transcriptome analysis using next generation sequencing

    55　(9)　841-846　2011/09

    Publisher: 医学書院

    DOI： 10.11477/mf.1542102720 　

    ISSN： 0485-1420

  128. 白色素胞を異所的に過形成するメダカ変異体ml‐3

    長尾勇佑, 足立朋子, 清水厚志, 関良子, 井上慎子, 亀井保博, 原郁代, 谷口善仁, 成瀬清, KELSH Robert, 若松佑子, 日比正彦, 橋本寿史

    日本動物学会大会予稿集　82nd　125　2011/08/20

  129. 次世代シークエンサーを使いこなす:目的別解析法からデータ処理まで ヒト・マウスの全エキソンリシークエンシングと疾患原因遺伝子の同定

    清水厚志

    細胞工学　30　(8)　808-814　2011/07/22

    Publisher: 学研メディカル秀潤社

    ISSN： 0287-3796

  130. P-395 ヒルシュスプルング病類縁疾患(hypoganglionosis)の原因遺伝子に関する考察(遺伝子・発生異常,ポスターセッション,第48回日本小児外科学会学術集会)

    下島 直樹, 清水 厚志, 古家 育子, 芝田 晋介, 岡野 ジェイムス 洋尚, 松尾 光一, 工藤 純, 岡野 栄之, 森川 康英

    日本小児外科学会雑誌　47　(4)　777-777　2011/07/05

    Publisher: 特定非営利活動法人日本小児外科学会

    DOI： 10.11164/jjsps.47.4_777_2 　

    ISSN： 0288-609X

  131. ヒルシュスプルング病類縁疾患(hypoganglionosis)の原因遺伝子に関する考察

    下島直樹, 清水厚志, 古家育子, 芝田晋介, 岡野ジェイムズ洋尚, 松尾光一, 工藤純, 岡野栄之, 森川康英

    日本小児外科学会雑誌　47　(4)　777-777　2011/07/05

    Publisher: 特定非営利活動法人 日本小児外科学会

    DOI： 10.11164/jjsps.47.4_777_2 　

    ISSN： 0288-609X

  132. イルカ味覚受容体遺伝子の構造と発現に関する研究

    徳永裕子, 渡邊壮一, 金子豊二, 徐泰健, 郷康広, 清水厚志, 伊藤春香, 徳武浩司, 内田詮三, 渡部終五, 浅川修一

    日本水産学会大会講演要旨集　2011　74　2011/03/27

  133. 特集を読むまえに 基礎の基礎 (特集 次世代シークエンサーを使いこなす--目的別解析法からデータ処理まで)

    清水 厚志, 佐々木 貴史

    細胞工学　30　(8)　790-795　2011

    Publisher: 学研メディカル秀潤社

    ISSN： 0287-3796

  134. Human and mouse whole exome resequencing to identify mutations

    Cell technology　30　(8)　808-814　2011

    Publisher: 学研メディカル秀潤社

    ISSN： 0287-3796

  135. 皮膚炎自然発症モデルマウスflaky tailの皮膚炎原因遺伝子の解明

    塩濱愛子, 佐々木貴史, 川崎洋, 清水厚志, 岡野栄之, 天谷雅行, 工藤純

    日本分子生物学会年会プログラム・要旨集(Web)　34th　WEB ONLY 2P-0819　2011

  136. ハダカデバネズミの分子生物学的研究の展開~社会性・ガン・老化研究のための新しいモデル動物~

    三浦恭子, 宮脇慎吾, 清水厚志, 八谷剛史, 関布美子, 疋島啓吾, 新井奈月, 土屋喜洋, 成田年, 榊原康文, 岡野栄之

    日本分子生物学会年会プログラム・要旨集(Web)　34th　WEB ONLY 1T16A-6　2011

  137. VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立に関する研究 VATER症候群の次世代シーケンサーによる遺伝子解析

    工藤純, 鳥居千春, 清水厚志

    VATER症候群の臨床診断基準の確立と新基準にもとづく有病率調査およびDNAバンク・iPS細胞の確立に関する研究 平成22年度 総括・分担研究報告書　25-27　2011

  138. CHARGE症候群の成人期の病像の解明と遺伝子診断の臨床応用・iPS細胞の確立に関する研究 CHARGE症候群の次世代シーケンサーによる遺伝子解析

    工藤純, 鳥居千春, 清水厚志

    CHARGE症候群の成人期の病像の解明と遺伝子診断の臨床応用・iPS細胞の確立に関する研究 平成22年度 総括・分担研究報告書　31-33　2011

  139. “ヒトゲノム”解読を貫徹する機能未知「カオナシ遺伝子」解明のメダカ作戦

    殿山泰弘, 清水厚志, 亀井保博, 清水淑子, 清水信義

    日本分子生物学会年会プログラム・要旨集(Web)　34th　WEB ONLY 2P-0123　2011

  140. Versican is Essential for Chamber Formation by Recruiting Cardiac Progenitor Cells from the Outflow Tract in Medaka Fish

    Sung Han Yoon, Shinji Makino, Atsushi Shimizu, Yuta Higashikuse, Mayumi Oda, Misato Fujita, Atsushi Kawakami, Akira Kudo, Shinsuke Yuasa, Motoaki Sano, Keiichi Fukuda

    CIRCULATION　122　(21)　2010/11

    ISSN： 0009-7322

  141. 次世代シーケンサーを用いたメダカ・トラフグ小分子RNAの発現解析

    浅川修一, チャニンヤー ウォンワランカナ, 寺井良太, 根来康介, 秋葉正毅, 小野陽介, 藤森一浩, 木下滋晴, 清水厚志, 堺弘介, 小島サビヌ和子, 満山進, 喜久里育也, 佐藤友紀, 照屋邦子, 城間亜紀乃, 照屋盛実, 鼠尾まい子, 矢野修一, 三輪友希乃, 今田有美, 塚原正俊, 工藤純, 平野隆, 清水信義, 渡部終五

    日本水産学会大会講演要旨集　2010　23　2010/09/22

  142. Removal of amino-terminal extracellular domains of desmoglein 1 by staphylococcal exfoliative toxin is sufficient to initiate epidermal blister formation

    Koji Nishifuji, Atsushi Shimizu, Akira Ishiko, Toshiroh Iwasaki, Masayuki Amagai

    JOURNAL OF DERMATOLOGICAL SCIENCE　59　(3)　184-191　2010/09

    DOI： 10.1016/j.jdermsci.2010.07.010 　

    ISSN： 0923-1811

  143. TlLLING法による遺伝子変異メダカの作製

    貴田 亨, 石川 智子, 清水 厚志, 亀井 保博, 殿山 泰弘, 藤堂 剛, 三輪 正直, 清水 信義

    比較内分泌学 = Comparative endocrinology　36　(137)　154-158　2010/05/31

    Publisher: 日本比較内分泌学会

    DOI： 10.5983/nl2008jsce.36.154 　

    ISSN： 1882-6636

  144. メダカ・トラフグ小分子RNAの次世代シーケンシング解析

    秋葉正毅, チャニンヤー ウォンワランカナ, 藤森一浩, 木下滋晴, 清水厚志, 堺弘介, 小島サビヌ和子, 満山進, 喜久里育也, 佐藤友紀, 照屋邦子, 城間亜紀乃, 照屋盛実, 鼠尾まい子, 矢野修一, 三輪友希乃, 今田有美, 塚原正俊, 工藤純, 平野隆, 清水信義, 渡部終五, 浅川修一

    日本水産学会大会講演要旨集　2010　133　2010/03/26

  145. メダカ変異体を使った個体レベルのゲノム研究の展望

    亀井 保博, 清水 厚志, 清水 信義

    比較内分泌学 = Comparative endocrinology　36　(136)　66-68　2010/02/28

    Publisher: 日本比較内分泌学会

    DOI： 10.5983/nl2008jsce.36.66 　

    ISSN： 1882-6636

  146. TILLING法による遺伝子変異メダカの作製

    貴田亨, 石川智子, 清水厚志, 亀井保博, 殿山泰弘, 藤堂剛, 三輪正直, 清水信義

    比較内分泌学　36　(137)　154-158 (J-STAGE)-158　2010

    Publisher: Japan Society for Comparative Endocrinology

    DOI： 10.5983/nl2008jsce.36.154 　

    ISSN： 1882-6636

  147. セグメント重複が霊長類の進化に果たした役割―ゲノム進化病としてのWilliams症候群―

    清水厚志

    生化学　ROMBUNNO.4W18-P-3　2010

    ISSN： 0037-1017

  148. 赤外レーザーによる遺伝子発現システム(IR‐LEGO)の様々なモデル生物への応用

    亀井保博, 浦和博子, 木村英二, 出口友則, 伊藤真理子, 北野健, 尾田正二, 殿山泰弘, 清水厚志, 三谷啓志, 八田公平, 清水信義, 岡田清孝, 弓場俊輔

    生化学　ROMBUNNO.1P-0388　2010

    ISSN： 0037-1017

  149. 心臓発生・分化の機序解明から新たな心不全治療開発へ

    牧野伸司, YOON Sung Han, 小田真由美, 東久世裕太, 清水厚志, 藤田深里, 川上厚志, 工藤明, 影山智己, 福田恵一

    生化学　ROMBUNNO.2W19-2　2010

    ISSN： 0037-1017

  150. メダカ変異体を使った個体レベルのゲノム研究の展望

    亀井保博, 清水厚志, 清水信義

    比較内分泌学　36　(136)　66-68 (J-STAGE)　2010

    DOI： 10.5983/nl2008jsce.36.66 　

    ISSN： 1882-6636

  151. メダカを用いたヒト疾患モデル

    清水 厚志

    比較内分泌学 日本比較内分泌学会　36　(139)　286-292　2010

    Publisher: Japan Society for Comparative Endocrinology

    DOI： 10.5983/nl2008jsce.36.286 　

    ISSN： 1882-6636 1882-6644

  152. クルマエビゲノムより見出した分節重複の解析

    小山喬, FAGUTAO Fernand F, RAPEEPAT Mavichak, SANTOS Mudjekeewis D, 藤加奈子, 片桐孝之, 坂本崇, 北門利英, 近藤秀裕, 青木宙, 廣野育生, 浅川修一, 清水厚志, 清水信義

    日本水産学会大会講演要旨集　2009　58　2009/09/30

  153. クルマエビゲノム中に見られた高頻度DNA断片の解析

    小山喬, 浅川修一, 片桐孝之, 清水厚志, FAGUTAO Fernand F, RAPEEPAT Mavichak, SANTOS Mudjekeewis D, 藤加奈子, 坂本崇, 近藤秀裕, 清水信義, 青木宙, 廣野育生

    マリンバイオテクノロジー学会大会講演要旨集　12th　83　2009/05/30

  154. 次世代シーケンサーを用いたメダカ・トラフグ小分子RNAの発現解析

    WONGWARANGKANA Chaninya, 秋葉正毅, 藤森一浩, 木下滋晴, 清水厚志, 堺弘介, 小島サビヌ和子, 満山進, 喜久里育也, 照屋盛実, 鼠尾まい子, 矢野修一, 三輪友希乃, 今田有美, 佐藤友紀, 塚原正俊, 工藤純, 平野隆, 清水信義, 渡部終五, 浅川修一

    日本分子生物学会年会講演要旨集　32nd　(Vol.1)　48　2009

  155. 熱ショック誘導Cre/loxシステムを活用したFOPモデルメダカの作製

    清水厚志, 清水信義

    日本分子生物学会年会講演要旨集　32nd　(Vol.4)　238　2009

  156. 進行性骨化性線維異形成症に関する疾患モデルメダカの作製

    清水厚志, 清水信義

    生化学　1P-1217　2008

    ISSN： 0037-1017

  157. 細胞分裂に関連したYPELファミリータンパク中の動物特異的メンバーYPEL5の性状解析

    細野克博, 蓑島伸生, 野田節子, 清水厚志, 佐々木貴史, 大坪正史, 清水信義

    生化学　3P-0499　2008

    ISSN： 0037-1017

  158. カオナシ遺伝子群の解析およびオンライン画像データベースの構築

    清水厚志, 浅川修一, 佐々木貴史, 清水信義

    生化学　4P-0931　2008

    ISSN： 0037-1017

  159. クルマエビゲノム中より見出された高頻度巨大配列の詳細な構造解析

    小山喬, 浅川修一, 片桐孝之, 清水厚志, 清水信義, FAGUTAO F. Fernand, RAPEEPAT Mavichak, SANTOS D. Mudjekeewis, 近藤秀裕, 青木宙, 廣野育生

    生化学　1P-1311　2008

    ISSN： 0037-1017

  160. 小胞輸送蛋白質GOLSYNの上皮系細胞におけるゴルジ体局在化の分子機構

    船越英資, 小田亮介, 清水厚志, 浅川修一, 清水信義, 伊藤文昭

    日本薬学会年会要旨集　127th　(2)　101　2007/03/05

    ISSN： 0918-9823

  161. The minimal eukaryotic ribosomal DNA units in the primitive red alga Cyanidioschyzon merolae

    Maruyama, S, Misumi, O, Ishii, Y, Asakawa, S, Shimizu, A, Sasaki, T, Matsuzaki, M, Shin-i, T, Nozaki, H, Kohara, Y, Shimizu, N, Kuroiwa, T

    Plant J　49　1122-1129　2007

    DOI： 10.1111/j.1365-313X.2006.03024.x 　

  162. アトピー性皮膚炎原因遺伝子フィラグリンのshotgun法による変異解析

    佐々木貴史, 工藤純, 海老原全, 塩濱愛子, 浅川修一, 高柳淳, 清水厚志, 渋谷和憲, 天谷雅行, 清水信義

    生化学　3P-1087　2007

    ISSN： 0037-1017

  163. カオナシ遺伝子群のノックダウン解析およびオンラインデータベースの構築

    清水厚志, 浅川修一, 佐々木貴史, 清水信義

    生化学　1P-0958　2007

    ISSN： 0037-1017

  164. 緑内障原因遺伝子候補領域7q35‐q36(GLC1F)のゲノム悉皆解析

    細野克博, 大坪正史, 清水厚志, 佐々木貴史, 堀田喜裕, 清水信義, 蓑島伸生

    生化学　1P-0586　2007

    ISSN： 0037-1017

  165. 連鎖解析による家族性聴覚障害の原因遺伝子探索

    石川サビヌ和子, 浅川修一, 清水厚志, 佐々木貴史, GUYOT Jean P, 石川烈, 枝松秀雄, 坂井真, 清水信義

    生化学　3P-1081　2007

    ISSN： 0037-1017

  166. 脳の構築と毛髪形成に関する遺伝子の比較

    浅川修一, 渋谷和憲, 清水厚志, 佐々木貴史, 工藤純, 清水信義

    日本医学会総会総会会誌　27th　68　2007

  167. 小胞輸送蛋白質GOLSYNのゴルジ体局在化機構

    船越英資, 小田亮介, 清水厚志, 浅川修一, 清水信義, 伊藤文昭

    生化学　3P-0340　2007

    ISSN： 0037-1017

  168. The DNA sequence of Medaka chromosome LG22

    Takashi Sasaki, Atsushi Shimizu, Sabine Kazuko Ishikawa, Shuichiro Imai, Shuichi Asakawa, Yuji Murayama, Heinz Himmelbauer, Hiroshi Mitani, Makoto Furutani-Seiki, Hisato Kondoh, Indrajit Nanda, Michael Schmid, Manfred Schartl, Masaru Nonaka, Hiroyuki Takeda, Hiroshi Hori, Akihiro Shima, Nobuyoshi Shimizu

    ZOOLOGICAL SCIENCE　22　(12)　1379-1379　2005/12

    ISSN： 0289-0003

  169. Characterization of the medaka Y-chromosome specific region

    Mariko Kondo, Indrajit Nanda, Ute Hornung, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Michael Schmid, Masaru Nonaka, Nobuyoshi Shimizu, Manfred Schartl

    ZOOLOGICAL SCIENCE　22　(12)　1509-1509　2005/12

    ISSN： 0289-0003

  170. 脊椎動物におけるCNR/Pcdh遺伝子クラスターの進化

    浅川修一, 石井靖幸, 佐々木貴史, 清水厚志, 多田基紀, 八木健, 清水信義

    日本分子生物学会年会講演要旨集　28th　170　2005/11/25

  171. メダカ染色体LG22の読解完了

    佐々木貴史, 清水厚志, 石川サビヌ和子, 今井周一郎, 浅川修一, 村山裕治, HIMMELBAUER Heinz, 三谷啓志, 古谷(清水)誠, 近藤寿人, INDRAJIT Nanda, SCHMID Michael, Schartl Manfred, 野中勝, 武田洋幸, 堀寛, 嶋昭紘, 清水信義

    日本分子生物学会年会講演要旨集　28th　51　2005/11/25

  172. メダカはいを用いたヒトカオナシ遺伝子群の解析

    清水厚志, 浅川修一, 佐々木貴史, 古谷(清木)誠, 近藤寿人, 清水信義

    日本分子生物学会年会講演要旨集　28th　127　2005/11/25

  173. メダカ・ゼブラフィッシュ間の遺伝子機能の進化比較によるWnt8の新しい機能の解明

    桃井章裕, 清水厚志, 長田優美, 佐々木貴史, 中島登, 三谷啓志, HIMMELBAUER Heinz, GEISLER Robert, 清水信義, 近藤寿人, 古谷(清木)誠

    日本分子生物学会年会講演要旨集　28th　126　2005/11/25

  174. 新規シンタフィリン類似蛋白質GOLSYNの細胞内局在

    船越英資, 浜野文子, 清水厚志, 浅川修一, 清水信義, 伊藤文昭

    日本薬学会年会要旨集　125th　(3)　84　2005/03/05

    ISSN： 0918-9823

  175. COH1 analysis and linkage study in two Japanese families with Cohen syndrome

    Kondo, I, A Shimizu, S Asakawa, K Miyamoto, H Yamagata, Y Tabara, N Shimizu

    CLINICAL GENETICS　67　(3)　270-272　2005/03

    DOI： 10.1111/j.1399-0004.2004.00396.x 　

    ISSN： 0009-9163

  176. Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence

    S Taudien, P Galgoczy, K Huse, K Reichwald, M Schilhabel, K Szafranski, A Shimizu, S Asakawa, A Frankish, IF Loncarevic, N Shimizu, R Siddiqui, M Platzer

    BMC GENOMICS　5　(92)　2004/12

    DOI： 10.1186/1471-2164-5-92 　

    ISSN： 1471-2164

  177. ゲノムシーケンスの解析に基づくヒト8番染色体q22‐qter領域の遺伝子地図作成

    山崎悟, 清水厚志, 石川サビヌ和子, 佐々木貴史, 工藤純, 蓑島伸生, 浅川修一, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　27th　504　2004/11/25

  178. ヒトゲノム“完成”配列の詳細かつ徹底的な解析によりヒト遺伝子の多様性を探る

    清水厚志, 浅川修一, 佐々木貴史, 山崎悟, 石川サビヌ和子, 工藤純, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　27th　410　2004/11/25

  179. 8番染色体q22‐qter領域のゲノム解析と疾患原因遺伝子の探索

    浅川修一, 清水厚志, 山崎悟, 石川サビヌ和子, 佐々木貴史, 工藤純, 山県英久, 蓑島伸生, 近藤郁子

    日本分子生物学会年会プログラム・講演要旨集　27th　504　2004/11/25

  180. マウス・メダカを用いたヒトDiGeorge症候群領域の比較ゲノム解析

    塩浜愛子, 佐々木貴史, 清水厚志, 蓑島伸生, 古谷(清木)誠, 近藤寿人, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　27th　509　2004/11/25

  181. メダカとフグの比較ゲノムによる配列の挿入欠失パターンの解明

    今井周一郎, 清水厚志, 佐々木貴史, 石川サビヌ和子, 浅川修一, 堀寛, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　27th　769　2004/11/25

  182. ヒト8番染色体q24.3領域にあるKIAA0014遺伝子のアンチセンス鎖にコードされる新規遺伝子LRRC24のクローニングとその発現解析

    石川サビヌ和子, 山崎悟, 清水厚志, 堺弘介, 浅川修一, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　27th　504　2004/11/25

  183. Finishing the euchromatic sequence of the human genome

    FS Collins, ES Lander, J Rogers, RH Waterston

    NATURE　431　(7011)　931-945　2004/10

    DOI： 10.1038/nature03001 　

    ISSN： 0028-0836

    eISSN： 1476-4687

  184. The minimal eukaryotic ribosomal DNA units in the primitive red alga Cyanidioschyzon merolae

    S Maruyama, O Misumi, Y Ishii, S Asakawa, A Shimizu, T Sasaki, MC Matsuzaki, T Shin-I, H Nozaki, Y Kohara, N Shimizu, T Kuroiwa

    DNA RESEARCH　11　(2)　83-91　2004/04

    DOI： 10.1093/dnares/11.2.83 　

    ISSN： 1340-2838

  185. メダカ・ミオシン重鎖遺伝子プロモーター領域の解析

    梁春実, 清水厚志, 佐々木貴史, 浅川修一, 清水信義, 渡辺終五

    日本水産学会大会講演要旨集　2004　205　2004/03/31

  186. Comparative genomics of the keratin-associated protein (KAP) gene clusters in human, chimpanzee, and baboon

    K Shibuya, J Kudoh, Obayashi, I, A Shimizu, T Sasaki, S Minoshima, N Shimizu

    MAMMALIAN GENOME　15　(3)　179-192　2004/03

    DOI： 10.1007/s00335-003-2313-9 　

    ISSN： 0938-8990

  187. ヒト8番染色体バンドq22‐qter55Mb領域の詳細な解析

    山崎悟, 浅川修一, 清水厚志, 石川サビヌ和子, 佐々木貴史, 工藤純, 蓑島伸生, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　26th　800　2003/11/25

  188. ヒトCSMD3遺伝子のゲノム構造解析およびメダカを用いた機能解析

    清水厚志, 浅川修一, 佐々木貴史, 山崎悟, 工藤純, 蓑島伸生, 近藤寿人, 古谷(清木)誠, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　26th　672　2003/11/25

  189. ヒト8番染色体シーケンシングの完成

    清水信義, 清水厚志, 山崎悟, 石川サビヌ和子, 村山裕治, 工藤純, 蓑島伸生, 佐々木貴史, 浅川修一

    日本分子生物学会年会プログラム・講演要旨集　26th　800　2003/11/25

  190. 8番染色体バンドq22‐q24.1領域にマップされた疾患原因遺伝子の探索。

    浅川修一, 清水厚志, 山崎悟, 佐々木貴史, 石川サビヌ和子, 工藤純, 山県英久, 蓑島伸生, 近藤郁子

    日本分子生物学会年会プログラム・講演要旨集　26th　1032　2003/11/25

  191. メダカ染色体LG22内の1Mb長領域の配列決定とそのシンテニー比較

    今井周一郎, 佐々木貴史, 清水厚志, 石川サビヌ和子, 浅川修一, 堀寛, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　26th　678　2003/11/25

  192. ヒトゲノム塩基配列の網羅的解析を基盤とした分子生命現象の探索: ヒト22番,21番,8番染色体を中心にして

    蓑島伸生, 工藤純, 浅川修一, 渋谷和憲, 佐々木貴史, 清水厚志, 山崎悟, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　26th　413　2003/11/25

  193. メダカとマウス,ヒトCNR/Pcdh遺伝子クラスターの比較ゲノム構造解析

    石井靖幸, 浅川修一, 佐々木貴史, 清水厚志, 八木健, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　26th　795　2003/11/25

  194. Detailed annotation and search for disease causing genes on 8q22-qter.

    S Asakawa, A Shimizu, S Yamazaki, SK Ishikawa, T Sasaki, J Kudoh, S Minoshima, Kondo, I, N Shimizu

    AMERICAN JOURNAL OF HUMAN GENETICS　73　(5)　432-432　2003/11

    ISSN： 0002-9297

  195. A novel giant gene CSMD3 encoding a protein with CUB and sushi multiple domains: a candidate gene for benign adult familial myoclonic epilepsy on human chromosome 8q23.3-q24.1

    A Shimizu, S Asakawa, T Sasaki, S Yamazaki, H Yamagata, J Kudoh, S Minoshima, Kondo, I, N Shimizu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　309　(1)　143-154　2003/09

    DOI： 10.1016/S0006-291X(03)01555-9 　

    ISSN： 0006-291X

  196. メダカWap65関連タンパク質の遺伝子構造解析とヘム結合能について

    平山真, 木下滋晴, 清水厚志, 佐々木貴史, 浅川修一, 清水信義, 渡部終五

    日本水産学会大会講演要旨集　2003　229　2003/04/01

  197. メダカ速筋ミオシン重鎖遺伝子の転写開始点付近の構造解析

    梁春実, 二瓶義明, 清水厚志, 佐々木貴史, 浅川修一, 清水信義, 渡部終五

    日本水産学会大会講演要旨集　2003　218　2003/04/01

  198. Genomic sequencing and analysis of the human chromosome 8q22-q24.1

    A Shimizu, S Asakawa, T Sasaki, S Yamazaki, S Ishikawa, J Kudoh, S Minoshima, N Shimizu

    AMERICAN JOURNAL OF HUMAN GENETICS　71　(4)　399-399　2002/10

    ISSN： 0002-9297

  199. Isolation of the full-length cDNAs for "predicted genes" and "novel genes" on human chromosome 21.

    J Kudoh, K Shibuya, J Wang, Obayashi, I, T Sasaki, A Shimizu, S Asakawa, S Minoshima, N Shimizu

    AMERICAN JOURNAL OF HUMAN GENETICS　71　(4)　396-396　2002/10

    ISSN： 0002-9297

  200. A duplicated copy of DMRT1 in the sex-determining region of the Y chromosome of the medaka, Oryzias latipes

    Nanda, I, M Kondo, U Hornung, S Asakawa, C Winkler, A Shimizu, ZH Shan, T Haaf, N Shimizu, A Shima, M Schmid, M Schartl

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　99　(18)　11778-11783　2002/09

    DOI： 10.1073/pnas.182314699 　

    ISSN： 0027-8424

  201. ゲノムシーケンスの解析に基づくヒト21番染色体の遺伝子地図の作成

    清水信義, 渋谷和憲, 大林泉, WANG J, 高橋未央, 川崎和彦, 佐々木貴史, 清水厚志, 工藤純

    生化学　74　(8)　739　2002/08/25

    ISSN： 0037-1017

  202. 野生型ビリルビンオキシダーゼと組み替え体の性質と反応ならびに活性部位近傍への変異導入

    藤田隆弘, 田中和浩, 張雷, 成瀬大作, 清水厚志, 鮫島達也, 山口庄太郎, 片岡邦重, 桜井武

    生化学　74　(8)　979　2002/08/25

    ISSN： 0037-1017

  203. ビリルビンオキシダーゼおよびそのミュータントの性質と酸素還元反応

    藤田隆弘, 清水厚志, 鮫島達也, 張雷, 片岡邦重, 桜井武

    金属の関与する生体関連反応シンポジウム講演要旨集　12th　102-103　2002/04/05

    ISSN： 0919-2093

  204. Molecular cloning of a member of the facilitative glucose transporter gene family GLUT11 (SLC2A11) and identification of transcription variants

    T Sasaki, S Minoshima, A Shiohama, A Shintani, A Shimizu, S Asakawa, K Kawasaki, N Shimizu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　289　(5)　1218-1224　2001/12

    DOI： 10.1006/bbrc.2001.6101 　

    ISSN： 0006-291X

  205. Isolation of the full-length cDNAs for "predicted genes" and finding "novel genes" on human chromosome 21.

    J Kudoh, K Shibuya, J Wang, Obayashi, I, M Tatsuyama, M Takahashi, K Kawasaki, A Shintani, T Sasaki, A Shimizu, S Asakawa, S Minoshima, N Shimizu

    AMERICAN JOURNAL OF HUMAN GENETICS　69　(4)　460-460　2001/10

    ISSN： 0002-9297

  206. The identification of disease genes by genomic sequencing analysis of 8q22-q24.

    N Shimizu, A Shimizu, T Sasaki, A Shintani, K Kawasaki, J Kudoh, S Minoshima, S Asakawa

    AMERICAN JOURNAL OF HUMAN GENETICS　69　(4)　458-458　2001/10

    ISSN： 0002-9297

  207. Properties and Reactivities of Bilirubin Oxidase Mutants.

    FUJITA TAKAHIRO, TANAKA KAZUHIRO, SHIMIZU ATSUSHI, SAMEJIMA TATSUYA, YAMAGUCHI SHOTARO, KATAOKA KUNISHIGE, SAKURAI TAKESHI

    錯体化学討論会講演要旨集　51st　537　2001/09/01

  208. The genomic structure and promoter region of the human Parkin gene

    S Asakawa, K Tsunematsu, A Takayanagi, T Sasaki, A Shimizu, A Shintani, K Kawasaki, AJ Mungall, S Beck, S Minoshima, N Shimizu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　286　(5)　863-868　2001/09

    DOI： 10.1006/bbrc.2001.5490 　

    ISSN： 0006-291X

  209. ビリルビンオキシダーゼの活性中心近傍への変異導入

    藤田隆弘, 田中和浩, 清水厚志, 鮫島達也, 山口庄太郎, 片岡邦重, 桜井武

    生化学　73　(8)　895　2001/08/25

    ISSN： 0037-1017

  210. マルチ銅オキシダーゼの構造遺伝子・活性中心・反応

    新田一朋, 藤田隆弘, 清水厚志, 鮫島達也, 桜井武

    金属の関与する生体関連反応シンポジウム講演要旨集　11th　120-121　2001/05/01

    ISSN： 0919-2093

  211. 家族性パーキンソン病原因遺伝子PARKINの構造解析と欠失変異のマッピング

    浅川修一, 服部信孝, 新谷愛, 佐々木貴史, 清水厚志, ZHANG J, 松峯宏人, 清水淑子, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　23rd　447　2000/11/25

  212. ヒト8番染色体q22‐23領域のシーケンシングと疾患遺伝子の探索

    清水厚志, 浅川修一, 川崎和彦, 蓑島伸生, 佐々木貴史, 新谷愛, 清水信義

    日本分子生物学会年会プログラム・講演要旨集　23rd　447　2000/11/25

  213. Enzyme Reaction Mechanism of Multicopper Oxidase.

    ZOPPELLARO G, SHIMIZU ATSUSHI, SAMEJIMA TATSUYA, SAKURAI TAKESHI

    酸化反応討論会講演要旨集　33rd　100-102　2000/10/20

  214. Molecular analysis of the deletion breakpoints of Parkin gene.

    S Asakawa, N Hattori, A Shintani, T Sasaki, K Kawasaki, A Shimizu, T Kitada, H Matsumine, S Minoshima, Y Shimizu, Y Mizuno, N Shimizu

    AMERICAN JOURNAL OF HUMAN GENETICS　67　(4)　398-398　2000/10

    ISSN： 0002-9297

  215. ラッカーゼおよびビリルビンオキシダーゼによる酸素の水への還元反応

    桜井武, ZOPPELLARO G, 山口庄太郎, 鮫島達也, 清水厚志

    生化学　72　(8)　873　2000/08/25

    ISSN： 0037-1017

  216. Myrothecium verrucaria bilirubin oxidase and its mutants for potential copper ligands

    A Shimizu, JH Kwon, T Sasaki, T Satoh, N Sakurai, T Sakurai, S Yamaguchi, T Samejima

    BIOCHEMISTRY　38　(10)　3034-3042　1999/03

    DOI： 10.1021/bi9819531 　

    ISSN： 0006-2960

  217. Elucidation of Functions for Copper Proteins in Terms of Genetic Engineering Approaches, As Exemplifying Bilirubin Oxidase.

    SAMEJIMA TATSUYA, SAKURAI TAKESHI, SHIMIZU ATSUSHI

    錯体化学討論会講演要旨集　47th　64　1997/09

  218. The role of copper ion and its ligands in bilirubin oxidase.

    SHIMIZU ATSUSHI, SAKURAI TAKESHI, SAMEJIMA TATSUYA

    錯体化学討論会講演要旨集　47th　37　1997/09

  219. On copper atom ligand and electron transfer pathway of a bilirubin oxidase.

    SHIMIZU ATSUSHI, SATO TAKANORI, SAKURAI TAKESHI, SAKURAI NORIHIKO, YAMAGUCHI SHOTARO

    日本分子生物学会年会プログラム・講演要旨集　19th　119-119　1996/07

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Books and Other Publications 7

  1. がんゲノムデータ解析

    清水厚志, 坊農秀雅

    メディカルサイエンスインターナショナル　2022/09/02

    ISBN: 4815730520

  2. 次世代シークエンサーDRY解析教本

    清水厚志, 坊農秀雅

    学研メディカル秀潤社　2019/12/12

    ISBN: 478090983X

  3. 次世代シークエンサーDRY解析教本 (細胞工学別冊)

    清水厚志, 坊農秀雅

    学研メディカル秀潤社　2015/10/15

    ISBN: 4780909201

  4. 細胞工学２０１１年８月号 Ｖｏｌ．３０ Ｎｏ．８

    清水厚志、佐々木貴史

    学研メディカル秀潤社　2011/07/19

    ISBN: 4780901219

  5. 実験医学増刊 Vol.35 No.17 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?

    山本 雅之, 荻島 創一

    羊土社　2017/10/23

    ISBN: 4758103666

  6. 実験医学別冊「次世代シークエンス解析スタンダード」ヒトゲノム・オミックス情報のコホート研究への応用.

    清水 厚志, 八谷 剛史, 田原 康玄

    羊土社　2014/08

  7. いまさら聞けない「遺伝医学」 (遺伝子医学MOOK別冊)

    斎藤, 加代子, 近藤, 恵里

    メディカルドゥ　2014/04/30

    ISBN: 4944157703

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Presentations 122

  1. 脳梗塞のゲノム疫学研究 Invited

    清水厚志

    第54回日本動脈硬化学会総会・学術集会　2022/07/24

  2. ポリジェニックリスクスコアのがん予防や治療への実装と課題 Invited

    日本人類遺伝学会第66回大会 第28回日本遺伝子診療学会大会 合同開催　2021/10/16

  3. 大規模ゲノムコホート連携と遺伝情報を活用した疾患発症リスク予測モデルによる個別化予防の実現 Invited

    清水厚志

    第123回 慶應義塾大学医学部生涯教育研修セミナー　2021/02/27

  4. いわて東北メディカル・メガバンク機構（IMM）におけるコホート検体の複合オミックス解析 Invited

    清水 厚志

    慶應義塾大学 システム医療研究開発センター セミナー　2016/01/29

  5. ヒトゲノム情報を活用した次世代型予防医療の実現に向けて Invited

    清水 厚志

    成育医療センター特別セミナー　2016/01/21

  6. NGS解析の基礎とゲノムコホート研究における血液検体のオミックス解析への応用 Invited

    清水 厚志

    NGS現場の会第四回研究会　2015/07/01

  7. 遺伝情報を用いた次世代型予防医療の実現のための技術的倫理的課題 Invited

    清水 厚志

    人間ドック学会「第２回遺伝子検査に関する検討委員会」　2015/06/12

  8. 東北MMB計画におけるバイオインフォマティクス

    清水 厚志

    AJACS岩手　2014/12/05

  9. 大規模疫学研究における３層オミックス解析 Invited

    八谷 剛史, 大桃 秀樹, 志波 優, 古川 亮平, 小野 加奈子, 清水 厚志

    第1回トランスオミクス研究会　2014/12/05

  10. ゲノム情報を用いた疾病発症予測に向けた技術的検討

    八谷 剛史, 清水 厚志

    理化学研究所セミナー　2014/11/26

  11. 大規模ゲノムコホートにおけるゲノムオミックス解析の実際 Invited

    清水 厚志

    アメリエフ 第35回次世代シーケンス解析・大勉強会　2014/09/22

  12. いわて東北メディカル・メガバンク機構（IMM）の目指す次世代型医療

    清水 厚志

    アジレントゲノミクスソリューション 遺伝子発現解析技術・データ解析セミナー　2014/02/06

  13. Retrotransposition of a unique piece of LCR7 played a key role in the generation of Williams-Beuren syndrome-associated LCR during the primate evolution.

    The International Congress of Human Genetics 12th Meeting and the American Society of Human Genetics 61th Annual Meeting,　2011

  14. Retrotransposition of a unique piece of LCR7 played a key role in the generation of Williams-Beuren syndrome-associated LCR during the primate evolution.

    The International Congress of Human Genetics 12th Meeting and the American Society of Human Genetics 61th Annual Meeting,　2011

  15. GOLSYN蛋白質の細胞内局在

    日本薬学会第125年会　2005

  16. Evolutionary Aspect of A Large Genome Size Difference Between Medaka and Fugu

    Medaka Genome and Vertebrate Evolution　2004

  17. Medaka LG22 Project: A Progress Report

    Medaka Genome and Vertebrate Evolution　2004

  18. Cadherin-related Neuronal Receptor/Protocadherin Gene Clusters in the Medaka Genome

    Medaka Genome and Vertebrate Evolution　2004

  19. Identification of 93 Hair Keratin-Associated Protein (KAP) Genes in Human Genome

    Cold Spring Harbor Labo. Meeting：The Biology of Genomes　2004

  20. Unvailing Human Kao-nashi (Face-less) Genes Using Medaka

    Cold Spring Harbor Labo. Meeting：The Biology of Genomes　2004

  21. MEDAKA LG22 PROJECT

    Cold Spring Harbor Labo. Meeting：The Biology of Genomes　2004

  22. Identification of 48 Hair Keratin-Associated Protein (KAP) Genes on Human Chromosome 21

    Expert Workshop on the Biology of Chromosome 21 Genes: Towards Gene-phenotype Correlations in Down syndrome　2004

  23. メダカとフグの比較ゲノムによるゲノムサイズの多様化の解明

    日本進化学会大会　2004

  24. Cohen症候群原因遺伝子COH1の日本人患者における変異解析

    日本遺伝子診療学会大会　2004

  25. 家族性パーキンソン病原因遺伝子Parkinの高頻度欠失変異形成の分子機構

    日本遺伝子診療学会大会　2004

  26. ヒトゲノムの情報から新しい生命現象発見の糸口をつかむ：22番、21番、８番染色体の実例

    日本遺伝子診療学会大会--シンポジウム１ ゲノム医科学１--　2004

  27. マウス涙腺および唾液腺細胞株のSAGEによる遺伝子発現解析

    日本遺伝子診療学会大会　2004

  28. ヒト8番染色体q22-qter領域52Ｍｂに存在する285個の遺伝子マップ

    日本遺伝子診療学会大会　2004

  29. Cohen症候群原因遺伝子COH1の日本人患者における変異解析

    第11回日本遺伝子診療学会大会　2004

  30. 家族性パーキンソン病原因遺伝子Parkinの高頻度欠失変異形成の分子機構

    第11回日本遺伝子診療学会大会　2004

  31. ヒトゲノムの情報から新しい生命現象発見の糸口をつかむ：22番、21番、８番染色体の実例

    第11回日本遺伝子診療学会大会--シンポジウム１ ゲノム医科学１--　2004

  32. Mutation screening of COH1 and BAFME on 8q22-q24.1

    The American Soc. Hum. Genet. Ann. Meeting　2004

  33. Identification of 93 Hair Keratin-associated Protein (KAP) Genes in Human Genome

    The American Soc. Hum. Genet. Ann. Meeting　2004

  34. A systematic approach for functional annotation of human KAO-NASHI (Face-less) genes

    The American Soc. Hum. Genet. Ann. Meeting　2004

  35. 8番染色体q22-q24.1領域にマップされた疾患原因遺伝子の探索

    日本人類遺伝学会大会　2004

  36. The Human KAO-NASHI (face-less) Genes: A Strategy for Systematic Characterization

    Cold Spring Harbor Meeting on Identification of Functional Elements in Mammalian Genomes　2004

  37. メダカとフグの比較ゲノムによる配列の挿入欠失パターンの解明

    日本分子生物学会年会　2004

  38. マウス・メダカを用いたヒトDiGeorge症候群領域の比較ゲノム解析

    日本分子生物学会年会　2004

  39. 8番染色体q22-qter領域のゲノム解析と疾患原因遺伝子の探索

    日本分子生物学会年会　2004

  40. ヒト8番染色体q24.3領域にあるKIAA0014遺伝子のアンチセンス鎖にコードされる新規遺伝子LRRC24のクローニングとその発現解析

    日本分子生物学会年会　2004

  41. ゲノムシーケンスの解析に基づくヒト8番染色体q22-qter領域の遺伝子地図作成

    日本分子生物学会年会　2004

  42. ヒトゲノム '完成' 配列の詳細かつ徹底的な解析によりヒト遺伝子の多様性を探る

    日本分子生物学会年会　2004

  43. The Genomic DNA Sequence of Medaka Chromosome LG22

    日本分子生物学会年会　2004

  44. Evolutionary Aspect of A Large Genome Size Difference Between Medaka and Fugu

    Medaka Genome and Vertebrate Evolution　2004

  45. Medaka LG22 Project: A Progress Report

    Medaka Genome and Vertebrate Evolution　2004

  46. Cadherin-related Neuronal Receptor/Protocadherin Gene Clusters in the Medaka Genome

    Medaka Genome and Vertebrate Evolution　2004

  47. Identification of 93 Hair Keratin-Associated Protein (KAP) Genes in Human Genome

    Cold Spring Harbor Labo. Meeting：The Biology of Genomes　2004

  48. Unvailing Human Kao-nashi (Face-less) Genes Using Medaka

    Cold Spring Harbor Labo. Meeting：The Biology of Genomes　2004

  49. MEDAKA LG22 PROJECT

    Cold Spring Harbor Labo. Meeting：The Biology of Genomes　2004

  50. Identification of 48 Hair Keratin-Associated Protein (KAP) Genes on Human Chromosome 21

    Expert Workshop on the Biology of Chromosome 21 Genes: Towards Gene-phenotype Correlations in Down syndrome　2004

  51. Mutation screening of COH1 and BAFME on 8q22-q24.1

    The American Soc. Hum. Genet. Ann. Meeting　2004

  52. Identification of 93 Hair Keratin-associated Protein (KAP) Genes in Human Genome

    The American Soc. Hum. Genet. Ann. Meeting　2004

  53. A systematic approach for functional annotation of human KAO-NASHI (Face-less) genes

    The American Soc. Hum. Genet. Ann. Meeting　2004

  54. The Human KAO-NASHI (face-less) Genes: A Strategy for Systematic Characterization

    Cold Spring Harbor Meeting on Identification of Functional Elements in Mammalian Genomes　2004

  55. The Genomic DNA Sequence of Medaka Chromosome LG22

    2004

  56. Structural analyses of medaka Wap65-1 and Wap65-2 genes and their heme binding ability

    Intl. Sympo. on Function of Marine Organisms -- Mechanisms of Adaptation to Diverse Environments --　2003

  57. Genomic structural analysis of the medaka fast skeletal myosin heavy chain genes

    Intl. Sympo. on Function of Marine Organisms -- Mechanisms of Adaptation to Diverse Environments --　2003

  58. メダカゲノムのシーケンシングと解読に向けて

    日本アクアゲノム研究会第7回シンポジウム　2003

  59. ヒト8番染色体q23領域に存在する新規遺伝子の同定

    日本薬学会第123回年会　2003

  60. メダカWap65関連タンパク質の遺伝子構造解析とヘム結合能について

    平成15年度日本水産学会大会　2003

  61. メダカ速筋ミオシン重鎖遺伝子の転写開始点付近の構造解析

    平成15年度日本水産学会大会　2003

  62. High Throughput Shotgun Library(HTSL) for the Complete Sequencing of the Medaka Genome

    'Cold Spring Harbor 68th Symposium ''The Genome of Homo Sapiens'''　2003

  63. Analysis of Human Chromosome 8Q22-Qter

    'Cold Spring Harbor 68th Symposium ''The Genome of Homo Sapiens'''　2003

  64. High Throughput Shotgun Library (HTSL) Towards Complete Sequencing of the Medaka Genome

    European Meeting on Zebrafish and Medaka Development and Genetics　2003

  65. Medaka Genome Mapping and Sequencing:A Novel Strategy Toward Complete Genome Sequence

    International Symposium on Aquatic Genomics　2003

  66. ヒト8番染色体上の疾患遺伝子座領域のゲノム解析

    日本人類遺伝学会第48回大会　2003

  67. Molecular Cloning and Characterization of Golgi-localized Syntaphilin-related Protein Gene (GOLSYN) on Human Chromosome 8q23

    Annual Meeting of the Japanese Biochemical Society　2003

  68. Detailed Annotation and Search for Disease Causing Genes on 8q22-qter

    The American Society of Human Genetics 53rd Annual Meeting　2003

  69. メダカ 染色体 LG22 内 の1Mb 長領域の配列決定とそのシンテニ−比較

    第26回日本分子生物学会年会　2003

  70. メダカ染色体LG22のシーケンシング：メダカゲノム完全シーケンスに向けて

    第26回日本分子生物学会年会　2003

  71. メダカとマウス、ヒトCNR/Pcdh遺伝子クラスターの比較ゲノム構造解析

    第26回日本分子生物学会年会　2003

  72. ヒト8番染色体バンドq22-qter55Mb領域の詳細な解析

    第26回日本分子生物学会年会　2003

  73. ヒトCSMD3遺伝子のゲノム構造解析およびメダカを用いた機能解析

    第26回日本分子生物学会年会　2003

  74. 8番染色体バンドq22-q24.1領域にマップされた疾患原因遺伝子の探索

    第26回日本分子生物学会年会　2003

  75. ヒトゲノム塩基配列の網羅的解析を基盤とした分子生命現象の探索：ヒト22番、21番、8番染色体を中心にして

    第26回日本分子生物学会年会　2003

  76. ヒト8番染色体シーケンシングの完成

    第26回日本分子生物学会年会　2003

  77. Structural analyses of medaka Wap65-1 and Wap65-2 genes and their heme binding ability

    Intl. Sympo. on Function of Marine Organisms -- Mechanisms of Adaptation to Diverse Environments --　2003

  78. Genomic structural analysis of the medaka fast skeletal myosin heavy chain genes

    Intl. Sympo. on Function of Marine Organisms -- Mechanisms of Adaptation to Diverse Environments --　2003

  79. High Throughput Shotgun Library(HTSL) for the Complete Sequencing of the Medaka Genome

    'Cold Spring Harbor 68th Symposium ''The Genome of Homo Sapiens'''　2003

  80. Analysis of Human Chromosome 8Q22-Qter

    'Cold Spring Harbor 68th Symposium ''The Genome of Homo Sapiens'''　2003

  81. High Throughput Shotgun Library (HTSL) Towards Complete Sequencing of the Medaka Genome

    European Meeting on Zebrafish and Medaka Development and Genetics　2003

  82. Medaka Genome Mapping and Sequencing:A Novel Strategy Toward Complete Genome Sequence

    International Symposium on Aquatic Genomics　2003

  83. Molecular Cloning and Characterization of Golgi-localized Syntaphilin-related Protein Gene (GOLSYN) on Human Chromosome 8q23

    Annual Meeting of the Japanese Biochemical Society　2003

  84. Detailed Annotation and Search for Disease Causing Genes on 8q22-qter

    The American Society of Human Genetics 53rd Annual Meeting　2003

  85. Genomic Sequencing and Detailed Analysis of The Human Chromosome 8q22-q24.1, The 2002 Meeting on GENOME SEQUENCING & BIOLOGY

    Meeting on Genome Sequencing & Biology　2002

  86. 馴化温度依存的に発現するメダカミオシン重鎖遺伝子のゲノム構造解析

    第8回小型魚類研究会　2002

  87. 8番染色体バンドq22－q24領域から同定された114個の遺伝子に関する網羅的変異検索

    第9回日本遺伝子診療学会大会　2002

  88. Isolation of the Full-length cDNAs for 'Predicted Genes' and 'Novel Genes' on Human Chromosome 21

    Annual Meeting of the American Society of Human Genetics (ASHG)　2002

  89. ゲノムシーケンスの解析に基づくヒト21番染色体の遺伝子地図の作成

    第75回日本生化学会大会　2002

  90. Genomic sequencing analysis of the human chromosome 8q22-q24.1

    Annual Meeting of the American Society of Human Genetics (ASHG)　2002

  91. 8番染 色体バンドq22－q24.1領域のゲノム解析による111個の遺伝子と65個の偽遺伝子の同定

    日本人類遺伝学会第47回大会　2002

  92. ゲノムシーケンスの解析に基づくヒト21番染色体の遺伝子地図の作成

    日本人類遺伝学会第47回大会　2002

  93. ヒト8番染色体q24.1-qter領域の物理地図作成とゲノムシーケンシング

    第25回日本分子生物学会年会　2002

  94. パーキンソン病の分子生物学：ういキンソン病の分子生物学―Parkin遺伝子の構造と変異解析

    第25回日本分子生物学会年会　2002

  95. ヒト21番染色体のゲノム配列に基づくcDNAの単離

    第25回日本分子生物学会年会　2002

  96. ヒト8番染色体q22-q24.1領域のシーケンシングと疾患遺伝子の探索

    第25回日本分子生物学会年会　2002

  97. ヒトゲノム塩基配列を読む －真の解読完了のために何が必要か：ヒト22番及び8番染色体のゲノム解析と遺伝子同定の現状―“網羅的”解析法の確立と実践

    第25回日本分子生物学会年会　2002

  98. Genomic Sequencing and Detailed Analysis of The Human Chromosome 8q22-q24.1, The 2002 Meeting on GENOME SEQUENCING & BIOLOGY

    Meeting on Genome Sequencing & Biology　2002

  99. Isolation of the Full-length cDNAs for 'Predicted Genes' and 'Novel Genes' on Human Chromosome 21

    Annual Meeting of the American Society of Human Genetics (ASHG)　2002

  100. Genomic sequencing analysis of the human chromosome 8q22-q24.1

    Annual Meeting of the American Society of Human Genetics (ASHG)　2002

  101. Genomic sequencing analysis of the jumbo gene Parkin of ~ 1.5 Mb

    HGM2001 (2001 ; Edinburgh)　2001

  102. Genomic sequencing analysis of human chromosome 8q21-q23

    HGM2001 (2001 ; Edinburgh)　2001

  103. Genomic sequencing and gene finding of human chromosome 8q21-q23

    Annual Meeting on Genome Sequencing & Biology (14th ; 2001 ; Cold Spring Harbor N.Y.)　2001

  104. Parkin遺伝子のゲノム構造とプロモーター解析

    第46回日本人類遺伝学会大会　2001

  105. ヒト21番染色体の全遺伝子解読へ向けて

    第46回日本人類遺伝学会大会　2001

  106. Isolation of the full-length cDNAs for 'Predicted Genes' and finding 'Novel Genes' on human chromosome 21

    The American Society of Human Genetics Annual Meeting (51st ; 2001 ; San Diego)　2001

  107. The identification of disease genes by genomic sequencing analysis of 8q22-q24

    The American Society of Human Genetics Annual Meeting (51st ; 2001 ; San Diego)　2001

  108. ヒト8番染色体8q22-q24領域の解析と疾患遺伝子の探索

    第46回日本人類遺伝学会大会　2001

  109. Parkin遺伝子のプロモーター解析

    第24回日本分子生物学会年会　2001

  110. ヒト8番染色体バンドq22-q24.1領域のゲノム解析

    第24回日本分子生物学会年会　2001

  111. ゲノムシーケンスの解析に基づくヒト21番染色体の遺伝子地図の作成

    第24回日本分子生物学会年会　2001

  112. ヒト8番染色体q22-q24.1領域のシーケンシングと疾患遺伝子の探索

    第24回日本分子生物学会年会　2001

  113. Genomic sequencing analysis of the jumbo gene Parkin of ~ 1.5 Mb

    HGM2001 (2001 ; Edinburgh)　2001

  114. Genomic sequencing analysis of human chromosome 8q21-q23

    HGM2001 (2001 ; Edinburgh)　2001

  115. Genomic sequencing and gene finding of human chromosome 8q21-q23

    Annual Meeting on Genome Sequencing & Biology (14th ; 2001 ; Cold Spring Harbor N.Y.)　2001

  116. Isolation of the full-length cDNAs for 'Predicted Genes' and finding 'Novel Genes' on human chromosome 21

    The American Society of Human Genetics Annual Meeting (51st ; 2001 ; San Diego)　2001

  117. The identification of disease genes by genomic sequencing analysis of 8q22-q24

    The American Society of Human Genetics Annual Meeting (51st ; 2001 ; San Diego)　2001

  118. 家族性パーキンソン病原因遺伝子PARKINの欠失変異の解析

    日本人類遺伝学会大会　2000

  119. Molecular Analysis of the Deletion Breakpoints of Parkin gene

    Annual Meeting of the American Society of Human Genetics (ASHG)　2000

  120. 家族性パーキンソン病原因遺伝子PARKINの構造解析と欠失変異のマッピング

    日本分子生物学会年会　2000

  121. ヒト8番染色体q22-23領域のシーケンシングと疾患遺伝子の探索

    日本分子生物学会年会　2000

  122. Molecular Analysis of the Deletion Breakpoints of Parkin gene

    Annual Meeting of the American Society of Human Genetics (ASHG)　2000

Show all Show first 5

Industrial Property Rights 2

  1. 腎細胞癌の診断マーカー及びそれを用いた診断方法

    大桃秀樹, 清水厚志, 金井弥栄, 新井恵吏

    特許7627904

    Property Type: Patent

  2. 脳梗塞発症リスクの予測モデル作成方法および予測方法

    八谷 剛史, 清水 厚志, 人見 次郎

    特許6716143

    Property Type: Patent

    Holder: 八谷 剛史;清水 厚志;人見 次郎

Research Projects 35

  1. DNAメチル化経時変化に基づく健康・老化状態の理解と介入ターゲットの探索

    小巻 翔平, 清水 厚志, 大桃 秀樹

    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: 岩手医科大学

    2025/04/01 - 2028/03/31

  2. Usefulness of metabolite biomarker as a common pathway for the prevention of non-communicable diseases and frailty

    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: Keio University

    2023/04/01 - 2028/03/31

  3. Platform of Supporting Cohort Study and Biospecimen Analysis

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Transformative Research Areas (platforms for Advanced Technologies and Research Resources)

    Category: Grant-in-Aid for Transformative Research Areas (platforms for Advanced Technologies and Research Resources)

    Institution: The University of Tokyo

    2022/04/01 - 2028/03/31

  4. マルチオミクスコホートデータベースを利活用した心不全重症化に関連する遺伝的リスク因子の解明 Competitive

    永井利幸, 清水厚志, 安斉俊久, 小柴生造, 櫻井 美佳, 須藤 洋一, 大桃 秀樹, 横田 勲, 天満 太郎, 中尾 元基, 三輪 芳久

    Offer Organization: 国立研究開発法人日本医療研究開発機構

    System: 日本医療研究開発機構研究費

    Category: 循環器疾患・糖尿病等生活習慣病対策実用化研究事業

    Institution: 北海道大学

    2025/04 - 2028/03

  5. ポリジェニックリスクスコアを用いた骨粗鬆症骨折発症予防プログラムの基盤構築

    大塚 弥生, 清水 厚志

    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: 岩手医科大学

    2023/04/01 - 2026/03/31

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    本研究の目的は日本人の骨量スコアのゲノムワイド関連解析（GWAS）から得られた多数の遺伝子多型の効果量に基づいて計算される多遺伝子スコア（Polygenic score、PGS）を計算し、PGSに基づく日本人の骨粗鬆症リスク予測モデルを開発することである。 本年度は東北メディカル・メガバンク計画地域住民コホート調査参加者約２万人をGWAS用（A群、10,794人）、PGSモデル調整用（B群、1,419人）、検証用（C群、7,621人）に分けて解析を行なった。まずA群の踵骨定量的超音波測定T-score値を目的変数として、性、年齢と遺伝子型11主成分を調整に用いてGWASを実施した。続いてGWASの結果から計37の候補PGSモデルを作成し、B群においてT-score値との相関に基づいて最良のモデルを選択した。骨粗鬆症の定義をT-score -2.5SD未満またはYAM 70%未満またはYAM 80%未満で、腰、上腕、大腿骨いずれかの骨折経験を持つ対象者とし、C群のベースライン調査情報を用いて同意撤回者と骨粗鬆症発症者を除外した5,927人をPGSに基づき五分位に層別化し、追跡調査期間における新規の骨粗鬆症発症率を解析した。その結果、42.7±9.5ヶ月の追跡調査期間に、577人が新規に骨粗鬆症を発症した。PGSの五分位により層別化して発症リスクを比較した結果、PGSが最も高い層を基準とすると最も低い層の骨粗鬆症の性年齢調整ハザード比は2.011（95%信頼区間、1.515～2.684）であり、遺伝的な骨粗鬆症発症高リスク者を早期にスクリーニングできることが示唆された。

  6. グループ化による膠原病の疾患横断的な遺伝的リスク要因の検出

    須藤 洋一, 清水 厚志

    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: 岩手医科大学

    2023/04/01 - 2026/03/31

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    本研究では、ヒト由来のゲノム・コホートデータを利用して研究を行う計画である。そのため、所属組織から研究計画について承認を得るとともに、倫理審査申請を行い研究倫理面での承認を得た。次いで、研究実施許可及び、解析に用いるスーパーコンピュータの利用許可を得た。また、免疫学、及びゲノム疫学分野における最新の情報を収集するため、書籍購入、及び免疫、ゲノム科学両分野の専門学会への参加を行った。本計画では将来的に日本ゲノムコホート連携を利用した大規模コホートデータ解析を想定しているため、連携を構成するコホートとの打ち合わせも実施した。 こうした許可申請や周辺環境の整備と並行して、可能な範囲から研究を開始した。まず、膠原病の関連解析やポリジェニックモデル作成に先立ち、研究アプローチや解析実施環境の構築・確認のため、重要かつ基本的な免疫学的形質である血中イムノグロブリン量についてのポリジェニックモデルを作成し、その精度評価を試みた。Pruning and Thresholding法 またはLDpred法等の手法により候補モデルを多数作成し、テストデータとの相関を基準として、最適なモデルを選択した。このモデルを用い、現在の利用可能なコホートデータ内でポリジェニックスコア（PGS）を計算した。次いで、計算したPGSと自己免疫疾患等多様な疾患リスクに対する網羅的な関連解析を実施した。このモデルの精度・特異度を明らかにするとともに、前向き検証も試み、疾患の予測性能を詳細に評価した。さらに計算されたPGSの分布に一般的でない特徴が見られたため、その原因調査を行った。これらの解析結果について取りまとめを行い、論文執筆に向けて準備を進めている。

  7. Development and Validation of a Combined Risk Prediction Model for Childhood Obesity Using Cord Blood Genomics and Epigenomics

    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: Iwate Medical University

    2023/04/01 - 2026/03/31

  8. Development and Validation of a Combined Risk Prediction Model for Childhood Obesity Using Cord Blood Genomics and Epigenomics

    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: Iwate Medical University

    2023/04/01 - 2026/03/31

  9. ヒトの網羅的解析とその統合解析による新型たばこの疾患リスクの早期評価とその展開

    原田 成, 清水 厚志, 大桃 秀樹

    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: 慶應義塾大学

    2022/04/01 - 2026/03/31

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    公衆衛生学上インパクトの大きな、新規環境要因によるがん等の疾患リスクに対し、早期に適切な対策を行うために、迅速かつ信頼性のあるリスク評価手法の開発が求められている。特に、加熱式たばこは使用者が急増しているが健康影響のエビデンスが少なく、迅速なリスク評価が必要である。そこで、疫学研究に網羅的解析（オミクス解析）を活用して新型たばこの疾患リスクを評価する方法として、まずは地域コホートで網羅的なDNAメチル化解析を実施することで、加熱式たばこ喫煙の健康影響のメカニズムと直結した複数のメチル化マーカーを明らかにし、リスク評価を行う対象者に網羅的DNAメチル化解析を実施し、加熱式たばこ使用および併用によるDNAメチル化の変動を明らかにしようとしている。 本研究では山形県鶴岡市で実施している住民コホート研究である、鶴岡メタボロームコホート研究への参加者のうち、2018年度の調査に参加した52名×4群（紙巻き、過去喫煙、非喫煙、加熱式）および紙巻き＋加熱式の併用者を対象者とする。Infinium MethylationEPIC BeadChip Kitを用い、DNAメチル化のマイクロアレイ解析を実施し、加熱式たばこの使用および併用によるDNAメチル化の変動を網羅的に明らかにするために、Kitによる測定を行っている。 また、この4群間のメタボロームの違いを明らかにし、加熱式たばこによる代謝動態への影響を示した。

  10. A comprehensive Mendelian Randomization on the causal pathway from psychological traits to all-cause mortality

    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 City University

    2022/04/01 - 2026/03/31

  11. A comprehensive Mendelian Randomization on the causal pathway from psychological traits to all-cause mortality

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Nagoya City University

    2022/04/01 - 2026/03/31

  12. ヒトの網羅的解析とその統合解析による新型たばこの疾患リスクの早期評価とその展開

    原田 成, 清水 厚志, 大桃 秀樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 慶應義塾大学

    2022/04/01 - 2026/03/31

  13. 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

  14. 周産期のストレス曝露に起因する児の知能・精神発達遅滞のバイオマーカー確立

    祖父江 憲治, 福本 健太郎, 真柳 平, 清水 厚志, 八木 淳子, 大桃 秀樹, 小巻 翔平, 赤坂 真奈美

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 岩手医科大学

    2021/04/01 - 2024/03/31

  15. Interdisciplinary fusion research for precision medicine in heart failure patients with preserved ejection fraction

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Hokkaido University

    2020/04/01 - 2024/03/31

  16. アルツハイマー病の未病・早期診断のためのDNAメチル化バイオマーカーの開発と検証

    佐々木 真理, 清水 厚志, 前田 哲也, 大桃 秀樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 岩手医科大学

    2020/04/01 - 2023/03/31

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    2020年度当初計画では（１）アルツハイマー病（AD）患者および対照群である健常高齢者の全血DNA・脳組織・遺伝子多型情報のブレインバンクからの分譲、（２）AD患者の全血DNAにおけるcommon DNA methylation variation (CDMV) に基づくDNAメチル化解析とエピゲノム関連解析（epigenome-wide association study; EWAS）によるAD患者特異的DNAメチル化マーカーの探索、（３）2021年度に実施を計画している地域住民コホートからのリクルートの準備、を予定していた。 本研究計画の実施にあたり、所属機関の機器利用申請、ならびに研究計画承認を受けた。続いて、岩手医科大学医学部倫理委員会へ審査申請し、承認を得た（受付番号: HG2020-023）。並行して国内複数のブレインバンクと生体試料の分譲を行っているコホートに検体や情報の分譲申請様式や手順を問い合わせ、申請書を作成した。また、東北メディカル・メガバンク計画地域住民コホート担当者と連携し、岩手県矢巾町在住のコホート参加者への本研究への案内文書の作成とインフォームドコンセント実施担当者の調整、会場の調整、採血および検体フローのマニュアルを作成した。

  17. コホート・生体試料支援プラットフォーム

    村上 善則, 今井 浩三, 若井 建志, 村上 善則, 松尾 恵太郎, 三上 春夫, 鈴木 貞夫, 喜多 義邦, 渡辺 能行, 田中 恵太郎, 嶽崎 俊郎, 栗木 清典, 古庄 憲浩, 有澤 孝吉, 玉腰 暁子, 今田 恒夫, 武林 亨, 三浦 克之, 成松 宏人, 鈴木 康司, 村山 繁雄, 高尾 昌樹, 赤津 裕康, 齊藤 祐子, 矢部 博興, 中杤 昌弘, 清水 厚志, 醍醐 弥太郎, 高橋 隆, 宮城 洋平, 渡邉 俊樹, 安井 寛, 田中 英夫, 内藤 真理子, 大中 佳三, 森 満, 川崎 良

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 新学術領域研究（研究領域提案型）『学術研究支援基盤形成』

    Category: 新学術領域研究（研究領域提案型）『学術研究支援基盤形成』

    Institution: 東京大学

    2016 - 2021

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    ①総括支援活動 : 若手支援研究成果発表会をオンラインで開催した(2021/2/9)。コホート・生体試料支援プラットフォーム(以下、CoBiA)の各支援機能の説明と教育講演に続き、31名の若手研究者がCoBiAの支援を受けて行った研究成果の発表と情報交換を行った。また、東北メディカル・メガバンク等国内4ゲノムコホート等と、日本多施設共同コーホート(J-MICC)研究の間で、共同研究の実施を合意するなど、わが国のゲノムコホート間の連携が進んだ。また日本疫学会のホームページでの告知、関連分野の科研費取得者へのダイレクトメールなど、研究支援の周知を図った。 ②コホートによるバイオリソース支援活動 : 今年度は291件の研究支援を実施した。またコホート(J-MICC)研究の追跡調査データ(死亡及びがん罹患。遺伝情報利用も含む)を用いた研究の解析テーマ募集を開始した。J-MICC研究において、新たにがん罹患追跡データを基盤として整備し、研究支援に供した。 ③ブレインリソースの整備と活用支援 : 大阪大学に本邦初のブレインバンク部門を創設し、大阪刀根山医療センター、宇多野病院、大阪府立母子医療センター、連合小児自閉症ゲノム・不死化細胞トリオ、法医学自殺レジストリを統合し、筋萎縮性側索硬化症エピゲノム研究等に貢献した。 ④生体試料による支援活動 : 298課題に生体機能分子の高感度解析・技術支援と共同研究ネットワーク構築支援を実施した。142課題にがん関連試料・情報(組織、血液)を提供した。7,774試料(血清、リンパ球、凍結組織、パラフィン包埋組織、DNA等)を収集し、3,581試料を提供した。ヒト試料解析研究の申請支援と病理形態学的解析支援を実施した。解析支援・連携構築支援・試料収集及び提供支援体制を強化した。学会・研究会及び公開講座を通じたヒト生体試料の活用研究の普及・啓発講演を実施した。

  18. Genetic factors of lifestyles and a cohort study for lifestyle-related diseases by Mendelian randomization

    WAKAI Kenji, KUBO Michiaki, HACHIYA Tsuyoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Nagoya University

    2015/04/01 - 2019/03/31

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    We examined genetic polymorphism related to lifestyle factors including exercise, stress coping, fat intake, and coffee consumption. The findings on exercise (rs10252228) and coffee consumption (rs2074356), in particular, were reproduced in independent samples. Mediation analysis was conducted for associations between alcohol consumption and stomach cancer risk by utilizing the SNPs that affect drinking habit (ALDH2 rs671 and ADH1B rs122984). The analysis suggested that acetaldehyde produced from ethanol was involved in increasing the risk of stomach cancer by alcohol drinking.

  19. Elucidation of the mechanism of cancer-resistance in the naked mole rat.

    Miura Kyoko, SHIMIZU Atsushi, OIWA Yuki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Hokkaido University

    2016/04/01 - 2018/03/31

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    The naked mole rat (NMR) is the longest-living rodent in the world and has extraordinary cancer-resistance. We studied the mechanisms of NMR-specific tumor-suppressive phenomenon, ASIS (ARF suppression-induced senescence). We performed mRNA-seq analyses and found the genes which are upregulated or downregulated upon ASIS induction. We also found NMR-specific regulation of signal transduction in ASIS.

  20. Mechanism of genomic stability of the naked mole rat

    Miura Kyoko, SHIMIZU ATSUSHI

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    2013/04/01 - 2016/03/31

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    Naked mole-rat (NMR) is one of only two eusocial mammals like ant or bee. NMR’s maximum lifespan exceeds 30 years although their body size is same as mouse. Moreover, these animals have never been observed any spontaneous tumor formation. The purpose of this study is to test whether NMR cells have the resistance to DNA damage or not. We treated the cells with mitomycin C or radiation, and found that NMR cells may have the resistance to acute DNA damage. Furthermore, we generated knock-in ES cells carrying NMR-gene X, which contribute to the DNA damage response, toward the generation of NMR-gene X knock-in mouse.

  21. Elucidation of novel genes causing auditory neuropathy

    MATSUNAGA Tatsuo, MIYA Fuyuki, MUTAI Hideki, KUDOH Jun

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)

    2012/04/01 - 2015/03/31

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    Auditory Neuropathy (AN) is a new concept of hearing loss with the clinical feature of poor recognition of words. The purpose of this study is to reveal novel genetic causes of AN. By Sanger sequencing analysis in 36 patients with AN, we detected 11 novel OTOF mutations in 25 patients and 1 known GJB2 mutation in a patient. By whole genome SNP analysis followed by real time PCR analysis in 4 patients with monoallelic OTOF mutations, we did not detect large deletions in OTOF. With exome analysis in 10 patients who had not been found genetic causes by previous genetic analyses, we detected 3 candidates of novel AN genes (PNPLA3, RYR3, TACC2) and a novel OPA1 mutation which is likely to be a de novo mutation.

  22. Study of responsible genes for cochlea and cochlear nerve dysplasia

    MATSUNAGA Tatsuo, SHIMIZU Atsushi, MIYA Fuyuki, MUTAI Hideki, KUDOU Jun, SUZUKI Naohiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    2012/04/01 - 2014/03/31

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    Cochlea dysplasia and the associated feature, cochlear nerve dysplasia have been difficult to provide clinical treatment, while the cause of the diseases is largely unknown. We conducted whole exome analysis of the families associated with these symptoms by Next Generation Sequencer and identified 2 novel candidate responsible genes. A candidate gene X appeared to be expressed in cochlear nerve, and was suggested to associate with neurite extension in our immunohistochemical and in vitro studies. The other candidate gene Y has already been shown to have significant role in inner ear development in mouse model, and was finally suggested to cause cochlea dysplasia in human in this study. Our results expanded our understanding of molecular pathology of cochlea and cochlear nerve dysplasia and will lead to development of better diagnosis and treatment.

  23. 対象配列特異的シークエンシング法によるドラフトゲノムの効率的精度向上法の確立 Competitive

    清水 厚志

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 慶應義塾大学

    2012/04/01 - 2013/03/31

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    次世代シークエンサーの台頭により、ゲノム配列が解読された生物種が急激に増加している。しかし、ヒト、マウスを除き、公開された概要（ドラフト）配列の精度は70%から90%にとどまり、モデル生物として確立されたラットやメダカ、ゼブラフィッシュなどのゲノム精度は利用している研究者のニーズを十分には満たしていない。そこで本研究計画ではメダカゲノムを解析対象に選定し、ドラフトゲノム配列の精度を向上させる手法を検討した。 平均冗長度x11のFosmidライブラリー末端配列データベースから５個のテロメア配列を含むクローンと３つのコントロールクローンを選定し、MiSeqのマルチプレックス法にて配列決定を行った。複数のソフトウェアでテロメアを含まないクローンのde novo アセンブルを行った結果、CLC Genomics WorkbenchとSOAPdenovoで完成配列を得ることができた。しかし、テロメア周辺のクローンには相同性の極めて高い（>99%）Low Copy Repeat（LCR）が存在したため、MiSeqのデータのみでは完成配列を得ることができなかった。そこで、平均2kb以上の長鎖DNA配列を得ることができるシークエンサーであるPacBio RSにより、配列決定を行い、先のデータと混合アセンブルをした結果、99%以上の相同性をもつLCRを正しく分離することが可能になり、完全長配列を得ることができた。以上の結果から混合アセンブルにより、複雑なゲノム構造をもつテロメア周辺クローンの配列決定が可能であると判断した。そこで、データベースからテロメア配列を含む240個のクローンの末端配列を抽出し、ユニークな配列をもつ12クローンを選抜してMiSeqとPacBio RSでシークエンシングを行った。現在、それぞれのクローンごとに配列解析中である。

  24. Overexpression of myogenic regulatory factors driven by heat shock promoters in medaka and its developmental study.

    SHIMIZU Atsushi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Keio University

    2010 - 2011

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    Fibrodysplasia ossificans progressiva(FOP) is a genetic disorder of dysregulated cellular differentiation which causes fibrous tissue(including muscle, tendon, and ligament) to be ossified when damaged. The mutations were identified in the activin A receptor, type I(ACVR1), a BMP type-1receptor. This study was purposed to establish the transgenic medaka fish that can induce overexpression of the ACVR1or BMP4gene by heat-shock in any target time points, tissues and cells. I established heat-shock inducible Cre recombinase expressing transgenic medaka fish(hsp70b :: Cre) using endogenous hsp70promoter and Cre inducible myogenic cells specific ACVR1expressing transgenic fish(DES :: lGlBMP4). However, both of heat-shock treated and non-treated double transgenic medaka fishes(hsp70b :: Cre and DES :: lGlBMP4) exhibited FOP like phenotypes, which mean endogenous hsp70 promoter was expressed continuously at a low level without heat induction. Then I combined the dual promoter expressing system and artificial heat-shock promoter and established heat-inducible double transgenic medaka fish(8xHSE :: Cre x DES : lGlACVR1).

  25. Comprehensive and functional analysis of Medaka small RNAs using next generation sequencer

    ASAKAWA Shuichi, FUJIMORI Kazuhiro, SHIMIZU Atsushi, SAKAI Kosuke, MITSUYAMA Susumu, KOJIMA SABINE Kazuko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: The University of Tokyo

    2009 - 2011

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    In this study, we analyzed the sequences of small RNAs(miRNA, piRNA, siRNA) extracted form tissues(Fast muscle, slow muscle, intestine, eye, brain, liver, ovary, testis, and embryos) of medaka(Oryzias latipes) and torafugu(Takifugu rubripes), and showed the expression profiles of the RNAs. In the tissues except for ovary and testis, the major species of expression were miRNAs, whereas in the ovary and testis, those were assumed to be piRNAs. There were found many unknown RNA species that were commonly expressed in medaka and torafugu

  26. Comparative genomics of chromosome rearrangement in vertebrates based on medaka genome information

    HORI Hiroshi, MITANI Hiroshi, SASAKI Takashi, SHIMIZU Atsushi, KANAMORI Akira

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Priority Areas

    Category: Grant-in-Aid for Scientific Research on Priority Areas

    Institution: Nagoya University

    2005 - 2009

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    Evolution of the genome size in vertebrates is often affected by changes in the noncoding sequences, for which insertions and deletions (indels) of small nucleotide sequences and amplification of repetitive elements are considered responsible. In this project, we especially compared the genomic DNA sequences of two kinds of fish, medaka (Oryzias latipes) and fugu (Takifugu rubripes), which show two-fold difference in the genome size (800 Mb vs. 400 Mb). We determined a contiguous DNA sequence of 790 kb from the medaka chromosome LG22 (linkage group 22). The sequence was aligned common between two fishes, and were found abundant in various repetitive elements including many types of unclassified low copy repeats, all of which accounted for more than a half (54%) of the genome size difference. These results strongly indicated that amplification of repetitive elements and compilation of indels are major driving forces to facilitate changes in the genome size.

  27. An Integrated Strategy for Unveiling the Function of KAONASHI Unknown (Functional) Genes

    SHIMIZU Nobuyoshi, ASAKAWA Shuichi, SHIMZU Atsushi, SASAKI Takashi, YO Go, SHIOHAMA Aiko, KOJIMA Sabinukazuko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Keio University

    2007 - 2008

  28. Construction of Fibrodysplasis Ossificans Progressiva Animal Model

    SHIMIZU Atsushi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Keio University

    2007 - 2008

  29. ヒトゲノム解析から発見した注目すべき8個の新規遺伝子の機能解析と医療への応用

    清水 信義, 塩濱 愛子, 清水 厚志

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特定領域研究

    Category: 特定領域研究

    Institution: 慶應義塾大学

    2006 - 2007

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    本研究では、永年のヒトゲノム解読から研究代表者らが発見した約300個の新規遺伝子の中から、特に興味深い疾患原因および疾患関連遺伝子8個(DGCR8、SGSM1、ZNF295、CSMD3、FFER1L6、PKHDIL1、DSCR4、VPS13B)を選抜し、比較ゲノム解析/トランスクリプトーム解析/プロテオーム解析/フェノーム解析に渡る総合的なアプローチを駆使して解析を行った。 DiGeorge症候群の原因遺伝子の一つとして我々が提唱してきたDGCR8に関しては。タンパクの強制発現と免疫染色の結果から、DGCR8がRNA干渉においてmiRNA形成過程で重要な役割を果たすというモデルを提唱した(Shiohama, A., et. al. Exp Cell Res.(2007))。 脳で強い発現を示すSGSMlについては、SGSMファミリーがいずれも脳で強い発現を示すこと、免疫沈降法の結果からRAPサブファミリーの全てとRAPIDモチーフを介して、RABサブファミリーの幾つかとTBCモチーフを介して結合することを明らかにした(Yang, H., et. al. Genomics.(2007))。 ZNF295は転写抑制因子であるが、ドーパミントランスポーター遺伝子の転写活性因子ZFP161と結合してその転写を抑制することを見出した。さらに、メダカのオルソログのノックダウン解析を行なったところ、脳全体の縮小と脳室の拡大が観察された。 ヒト胎盤にのみ検出されるDSCR4については、欠失変異体を用いたプロモーター活性を測定し、nt-800付近で著しい活性の上昇と抑制を示す塩基配列を見出した(Asai, S., et. al. Biochim Biophys Acta.(2008))。 その他3つの遺伝子に関しても進化上重要となる数種のゲノムを用いた比較ゲノム解析、ヒト・メダカを用いた発現解析、ノックダウン解析を行った。

  30. Comprehensive analysis of 300 KAO-NASHI (Face less) genes.

    SHIMIZU Nobuyoshi, ASAKAWA Shuichi, SHIMIZU Atsushi, SASAKI Takashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: KEIO UNIVERSITY

    2005 - 2006

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    The human genome project has provided a computer-estimation of 23,000 protein-coding genes in the human genome. However, many of these protein-coding genes are not fully proven for their existence by experimental evidence. In general, proteins with known motifs are readily classified, but substantial numbers of protein have no obvious motifs in their sequences. We designated these genes/proteins without obvious motifs as KAO-NASHI (Face-less) and initiated a project to unveil their face (kao) by comparative genomics and knock-down analysis. We extracted 1,000 KAO-NASHI genes from human genome sequence by step-wise filtration with InterPro motif analysis, BLAST homology search and PubMed document search. A small fish medaka (Oryzias latipes) was chosen as an experimental system to knock-down medaka orthologs of human KAO-NASHI genes with morpholino-antisense oligos. As an initial study, we designed antisense oligos to target translation initiation sites of 130 medaka kao-nashi genes. When these antisense oligos were micro-injected into medaka embryos, their morphogenesis at early developmental stages was disturbed and morphological changes were observed at certain rates. Thus, we obtained initial sketchy information how these medaka kao-nashi genes are involved in the embryonic process of patterning and organ formation. To date, 60 genes were found to cause embryonic defects and these were further classified in terms of developmental sub-stages and expression profiles. Thus, our approach using medaka seems effective and it will eventually provide functional information on the human KAO-NASHI genes/proteins.

  31. 機能未知(カオナシ)遺伝子群のインフォマティクスとノックダウン法を駆使した解析

    清水 厚志

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特定領域研究

    Category: 特定領域研究

    Institution: 慶應義塾大学

    2005 - 2005

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    1)データベースの構築 1000個のカオナシ遺伝子についてデータベースを構築し相同性のある遺伝子および他の生物種の相同遺伝子のデータをBLASTを用いて集積するシステムを立ち上げた。ヒトカオナシ遺伝子に関しては、cDNAの増幅のために必要なゲノム構造の入力を行いプライマーの設計も自動で行うシステムを構築した。設計した20個のモルフォリノアンチセンスオリゴ(MO)の配列データおよび位置の登録を行った。RT-PCRの結果やメダカ胚の画像、条件などをインジェクション機器に付属したPCからデータベースにアップロードするシステムを構築した。さらに、これらのデータをウェブブラウザーで表示できるシステム構築を行った。 2)カオナシ遣伝子に対するRT-PCR及びWhole mount in situ法による発生初期ステージの発現解析 メダカの発生ステージごとに受精卵を100-1000個採取しmRNAを抽出しcDNAを合成した。これらのcDNAライブラリーを用いて130個のヒトカオナシ遺伝子のメダカオルソログのRT-PCRによる発現解析を行った。これらの発現情報をもとにMOが有効な初期胚から発現している遺伝子20個をノックダウン解析の対象遺伝子とした。 3)ノックダウン法による機能解析 2)で選択した20個のカオナシ遺伝子についてMOを作製しメダカ初期胚に対しノックダウンを行った。その結果、脳室の肥大、発生阻害、アポトーシスなどを引き起こすMOを得ることができた。これらのことから機能推定が全くできず逆遺伝学の対象から外れているカオナシ遺伝子の中に発生に関与する遺伝子が含まれていることが確認できた。 一方で、より安価にノックダウン解析を進めるためMOの他に市販されているアンチセンスオリゴであるGripNAやLNAなどを用いてノックダウン解析を行ったがMOと同様の表現型を得ることができなかった。

  32. ヒトゲノム解読から発見した注目すべき8個の新規遺伝子の機能解析と医療への応用

    清水 信義, 清水 厚志, 塩濱 愛子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特定領域研究

    Category: 特定領域研究

    Institution: 慶應義塾大学

    2005 - 2005

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    1:DGCR8は1つのWWドメインと2つのDSRBドメインを併せ持った極めて稀な構造を持つタンパク質を産生する。マウス胎児を用いた解析で、DiGeorge/CAFS症候群の発症組織に一致する発現を認めた。 2:LLN12(RUTBC2)は特に脳で強い発現を示しており機能が注目される。RUTBCの全長クローニング、発現系の構築を行った。 3:ZNF295はBTB/POZドメインとZincフィンガードメインを持つ。ドーパミントランスポーター(DAT)遺伝子の転写を促進することが知られているZFP161タンパクと結合して転写を抑制することを発見した。 4:C8orfK23(FER1L5)は新規遺伝子であり巨大タンパク質をつくることが判明した。ホモローグ検索の結果、非症候群性難聴DFNB9の原因遺伝子OTOFにもっとも類似していた。 5:CSMD3は連鎖解析により良性の家族性てんかんの原因候補遺伝子と考えられる。CSMDファミリーは脳で強く発現しているが、8番染色体の解析の結果CSMD1は多様性が極めて高いことが判明した。 6:PKHD1L1は多発性嚢胞腎(ARPKD)の原因遺伝子であるPKHD1のファミリー遺伝子である。モデル生物としてメダカを選択し、RT-PCRにより67エキソンの配列決定を行うことができた。 7:DSCR4はヒト組織の中では胎盤にのみ検出されるが、マウス胎盤には検出されないという極めてまれなタンパク質である。転写開始点を含む一連の欠失体を作製し、活性を測定したところnt-800付近の領域で著しい活性の上昇が見られた。 8:COH1(VPS13B)はCohen症候群の原因遺伝子として確認された巨大タンパク質である。VSP13Aは舞踏病・有棘赤血球症の原因遺伝子であることから、VSP13ファミリーのすべてが何らかの重要な生理作用を営んでいると考える。

  33. モデル生物であるメダカを活用したCohen症候群原因遺伝子の機能解析

    清水 厚志

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 若手研究(B)

    Category: 若手研究(B)

    Institution: 慶應義塾大学

    2004 - 2005

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    1:比較ゲノム解析 8番染色体長腕部(8q22.2)に位置するCohen症候群の原因遺伝子COH1の機能解明のため、本研究での主な対象であるメダカのCoh1遺伝子の解析および単離を行った。昨年度行った詳細なコンピュータプログラムによるエキソン予測などにより、各生物種におけるCOH1遺伝子のゲノム上でのサイズはヒト830kb、イヌ750kb、ラット620kb、マウス560kb、ニワトリ420kb、メダカ400kb、フグ230kb、ショウジョウバエ12kbであることがわかった。また、エキソン28の2つのバリアントのうち長いエキソン28はマウスおよびラットのみで欠損していること、鳥類からヒトまではCOH1遺伝子は62個のエキソンで構成されているが魚類においてエキソン29、34、42、61が2個に、エキソン56は3個に分断されていることが判明した。 2:ノックダウン解析 メダカ初期胚からRNAを抽出し、RT-PCRによりメダカCoh1のクローニングを行った。RT-PCRの結果からはメダカ初期胚においてCoh1の発現量は低く発生に伴い発現量が増加することが確認できた。続いて空間的な発現を確認するためクローニングしたCoh1遺伝子の3'側の部分配列を用いてメダカ初期胚のWhole-mount in situ hybridizationを行ったが明瞭なシグナルを検出することはできなかった。そこで、Coh1遺伝子の複数ヶ所にモルフォリノアンチセンスオリゴ(MO)を設計し、メダカ胚へのマイクロインジェクションによりノックダウン解析を行った。他の遺伝子のノックダウン解析で文献に記載されている濃度でインジェクションを行った場合は、配列を一部置き換えたコントロールMOでも発生の遅れが見られたため、低濃度条件でインジェクションした。その結果、極少数の胚で発生の遅延や形態不全が見られた。

  34. 慢性型開放隅角緑内症(GLC1D)の原因遺伝子の探索・解析

    清水 厚志

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 若手研究(B)

    Category: 若手研究(B)

    Institution: 慶應義塾大学

    2002 - 2003

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    8番染色体長腕q23にマップされている慢性型開放隅角緑内障の原因遺伝子の同定のため、昨年度に引き続き網羅的遺伝子同定を進めるとともに、緑内障患者DMを用いてマップした領域内の全遺伝子の変異検索を試みた。 同疾患原因遺伝子の候補領域(DNAマーカーD8S556からD8S522)をカバーする10Mbの塩基配列に対し公共データベースを用いたホモロジー検索、フグゲノム、マウスゲノムとの比較、およびコンピュータプログラムによるエキソン予測などを駆使して解析を行い、新規遺伝子に対しては非翻訳領域を含む全長構造決定とともに発現プロファイル解析等を行った。その結果、新規遺伝子を含む25個の遺伝子の存在を本領域に確認することができた。特に新規に発見されたPKHD1L1およびCSMD3はそれぞれエキソン数が約70の巨大遺伝子であった。これら2つの巨大遺伝子を含む25個の遺伝子のエキソン・イントロン構造を解析し、得られた位置情報を元に全エキソンを増幅する約300セットのプライマーを設計した。また、エキソン長が300bpを超えている場合には、分割してプライマーを設計し、それぞれが300bp程度になるように調節した。これらのプライマーを用いて米国との共同研究により同領域内に原因遺伝子がマップされている緑内障患者DNAに対して変異検索を行った。その結果多数のSNPsの存在が確認され、複数のSNPsにおいてアミノ酸置換が確認できた。しかしながら現在、これらのSNPsと緑内障との関連性は見いだされていない。

  35. Fine analysis of low copy repeat sequences which cause diseases by chromosomal microdeletion/microduplication and complete identification of content genes within them

    MINOSHIMA Shinsei, SHIMIZU Atsushi, SASAKI Takashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Keio University

    2001 - 2002

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    There exist a class of sequences Low Copy Repeats (LCRs) in human genome. LCRs are not ordinary repetitive sequences, but consist of various units such as genes, pseudogenes and their fragments. It is considered that LCRs have been formed by duplication, inversion and deletion of those units together with surrounding sequences during the evolution. LCR-mediated dynamic change of human genome is one of mechanisms for generation of copy number variation (CNV). CNVs occasionally cause diseases such as DiGeorge syndrome and Smith-Magenis syndrome. Responsible regions of those diseases are usually surrounded by LCRs. CNVs are thought to be associated with many other genetic diseases and some of mental diseases, and are being extensively investigated. LCRs are also one of the important factors of sequence gaps in human genome. Thus, CNV and LCRs are important targets of current genome research and its medical application. Here, we analyzed LCRs in Williams syndrome region (WBSCR) on 7q11.23 and 8p23.1 duplication syndrome. All of sequence data of these regions in NCBI build 36 were obtained and manually re-analyzed to construct more precise sequence contigs. Position of various LCR units and genes/pseudogenes in LCR units were identified. Comparative analyses using primate genomes strongly suggested that in both disease regions a core unit sequence existed in a common ancestor genome, and that in various events during evolution the core sequence enveloped surrounding sequences and made them a new class of LCRs. Also, we indicated that a sequence gap within WBSCR (7q11.23) in build 36 is actually not a gap, which was introduced because of co-existence of 2 different alleles with CNVs. The gap has been cleared up by separating these BAC clones into 2 alleles. These results were reported also in the following papers after the term of project: Nature 431:931,2004; BMC Genomics 5:92,2004; Nature 439:331,2006.

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Teaching Experience 8

  1. メディカルゲノミクス　岩手医科大学

  2. 生命科学解析手法概論　岩手医科大学

  3. 物質・生物機能科学特別講義　日本女子大学

  4. 分子遺伝学　慶應義塾大学

  5. ゲノム科学　慶應義塾大学

  6. 水圏生命科学特論　東京大学

  7. ゲノムコホート研究・生体情報解析学　岩手医科大学

  8. 分子生物学　慶應義塾大学, 岩手医科大学

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Social Activities 3

  1. 遺伝と病気（いでんとびょうき）

    第４回ゲノムコホート研究における遺伝統計学公開市民講座

    2019/11/16 -

  2. 遺伝講習会

    岩手医科大学矢巾キャンパス

    2014/11/01 -

  3. 遺伝講習会

    岩手県立大船渡病院

    2015/02/14 -

Media Coverage 6

  1. 日本人の病気共同研究 環境や遺伝 36万人分データ利用

    読売新聞岩手版

    2021/08

    Type: Newspaper, magazine

  2. DNAメチル化 Myself

    バイリンガルニュース

    2017/07/13

    Type: Internet

  3. DNA methylation analysis to decipher epigenomic diversity Myself

    The Science News

    2017/05/12

    Type: Newspaper, magazine

  4. 脳梗塞なりやすさゲノム予測 岩手医科大が新手法

    朝日新聞

    2017/01/20

    Type: Newspaper, magazine

  5. KDDI総研とIMM健康寿命延伸へ共同研究開始

    科学新聞

    2021/03/05

    Type: Newspaper, magazine

  6. 脳梗塞リスク予測 遺伝子との関連分析 予防に寄与する可能性

    岩手日報

    2017/01/20

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