研究者詳細

顔写真

オオモモ　ヒデキ
大桃　秀樹
Hideki Ohmomo
所属
東北メディカル・メガバンク機構　医療情報ＩＣＴ部門
職名
准教授
学位

  • 博士（神経科学）（筑波大学）

  • 修士（神経科学）（筑波大学）

研究分野 1

  • ライフサイエンス / ゲノム生物学 / DNAメチル化解析、遺伝子発現解析、バイオバンク

論文 63

  1. Inter-individual differentially methylated region-targeted EWAS reveals epigenetic signatures of early childhood adversity 査読有り

    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　2026年1月2日

    DOI： 10.1080/17501911.2026.2613008 　

  2. Population attributable fraction of all-cause mortality due to non-normal blood pressure: results from the 2013 to 2016 baseline survey of the TMM CommCohort Study. 査読有り

    Hatanaka R, Nakaya N, Kogure M, Nakaya K, Chiba I, Tokioka S, Takase M, Kotozaki Y, Obara T, Nagaie S, Ohmomo H, Nasu T, Satoh M, Murakami T, Metoki H, Hamanaka Y, Orui M, Kodama EN, Fuse N, Izumi Y, Tanno K, Hozawa A

    Hypertension research : official journal of the Japanese Society of Hypertension　2025年11月12日

    DOI： 10.1038/s41440-025-02436-0 　

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

  3. 東日本大震災による住宅被害の程度と全死亡リスク 東北メディカル・メガバンク計画

    中谷 直樹, 中谷 久美, 小暮 真奈, 事崎 由佳, 畑中 里衣子, 千葉 一平, 時岡 紗由理, 高瀬 雅仁, 永家 聖, 大桃 秀樹, 那須 崇人, 布施 昇男, 寳澤 篤, 丹野 高三

    日本公衆衛生学会総会抄録集　84回　436-436　2025年10月

    出版者・発行元： (一社)日本公衆衛生学会

    ISSN：1347-8060

  4. Study Profile of the Iwate PGS Assessment and Risk Communication (PARC) Study. 査読有り

    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年9月6日

    DOI： 10.2188/jea.JE20250078 　

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    BACKGROUND: The potential impacts of polygenic scores (PGS) on health-behavior changes are not fully understood. The Iwate PGS Assessment and Risk Communication Study aims to investigate the effects of reporting PGS-based risk for ischemic stroke on health behaviors. METHODS: Participants wishing to know their PGS-based ischemic stroke risk were recruited from health checkup venues for workers in Iwate Prefecture in 2023. Health checkup data, biospecimens, and questionnaire responses were collected for biochemical testing, genotyping, and storage in the Tohoku Medical Megabank integrated biobank. The risk was calculated using an integrative PGS model for East Asians. Participants were randomly assigned to two groups, and one group received their risk report as the intervention group. The impacts of the risk notification will be investigated in follow-up surveys. RESULTS: Of 3,599 workers, 2,088 participated in the study (consent rate, 58.0%). The demographic profile of the eligible 2,083 participants was as follows: 80.7% males, and dominance of participants aged 18-29 years (25.2%), in their 30's (25.3%), and in their 40's (24.7%). Two hundred participants (9.7%) had a risk of 1.0 as the reference; 57 (2.7%), 927 (44.7%), and 888 (42.9%) participants had 2.1-3.4-, 1.4-1.9-, and <1.0-fold that risk, respectively. CONCLUSION: We collected health information and biospecimens from over 2,000 workers, and disclosed the PGS-based ischemic stroke risk. Behavioral effects will be evaluated 1 year after disclosure, with follow-up until 2030. As Japan's first large-scale PGS risk communication study, it will provide initial insights for implementing PGS in personalized preventive medicine.

  5. Mapping the human epigenetic landscape across three generations: A DNA methylation resource from TMM BirThree

    Atsushi Shimizu, Shiori Minabe, Hideki Ohmomo, Akira Takashima, Kanako Ono, Takako Aoyama, Kumi Furusawa, Shohei Komaki, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, So Umekage, Erika Kurokawa, Kotoka Kikuchi, Gen Haba, Miyuki Terata, Chizuko Isurugi, Hanae Kawamura, Takanori Sato, Shinya Hatayama, Rie Oyama, Tsukasa Baba, Shu Tadaka, Satoshi Mizuno, Mami Ishikuro, Hisaaki Kudo, Taku Obara, Kazuki Kumada, Fumiki Katsuoka, Soichi Ogishima, Kengo Kinoshita, Masayuki Yamamoto, Shinichi Kuriyama

    2025年8月20日

    DOI： 10.21203/rs.3.rs-7314319/v1 　

  6. Exploring novel blood-based DNA methylation biomarkers for alzheimer's disease via targeted sequencing of highly variable CpG sites. 国際誌 査読有り

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

    BMC research notes　18　(1)　350-350　2025年8月12日

    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.

  7. Genetic predisposition for immunoglobulin E production explains atopic risk in children: Tohoku Medical Megabank cohort study 査読有り

    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

    The American Journal of Human Genetics　2025年7月

    DOI： 10.1016/j.ajhg.2025.06.015 　

    ISSN：0002-9297

  8. Genome-wide association study of plasma amino acids and Mendelian randomization for cardiometabolic traits 査読有り

    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　2025年4月25日

    DOI： 10.1038/s41598-025-98992-z 　

    ISSN：2045-2322

  9. Profiling of runs of homozygosity from whole-genome sequence data in Japanese biobank 査読有り

    Aye Ko Ko Minn, Motomichi Matsuzaki, Akira Narita, Takamitsu Funayama, Yurii Kotsar, Satoshi Makino, Jun Takayama, Tohoku Medical Megabank Project Study Group, Hikaru Abe, Michiaki Abe, Momoka Abe, Naomi Abe, Noriko Abe, Tomomi Abe, Yuto Abe, Shizuko Ahiko, Kayo Aiki, Hiromi Aizawa, Yukari Akiyama, Hayato Anzawa, Eri Aoki, Yuichi Aoki, Hiroko Arai, Misaki Arakawa, Yukie Asano, Liam Baird, Ayano Chiba, Haruna Chiba, Ippei Chiba, Kenji Chiba, Keiko Chida, Inaho Danjoh, Hisako Endo, Reika Fue, Futaba Fujishiro, Yayoi Fujita, Waka Fukunaga, Takuo Fukushi, Mami Funata, Takamitsu Funayama, Sho Furuhashi, Nobuo Fuse, Kumiko Fushiya, Tomomi Gamo, Chinatsu Gocho, Katsuhiro Gonoi, Maki Goto, Takahiko Goto, Yukie Goto, Kaori Gouko, Michiko Haga

    Journal of Human Genetics　2025年4月3日

    DOI： 10.1038/s10038-025-01331-3 　

    ISSN：1434-5161 1435-232X

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    <jats:title>Abstract</jats:title> <jats:p>Runs of homozygosity (ROHs) are widely observed across the genomes of various species and have been reported to be associated with many traits and common diseases, as well as rare recessive diseases, in human populations. Although single nucleotide polymorphism (SNP) array data have been used in previous studies on ROHs, recent advances in whole-genome sequencing (WGS) technologies and the development of nationwide cohorts/biobanks are making high-density genomic data increasingly available, and it is consequently becoming more feasible to detect ROHs at higher resolution. In the study, we searched for ROHs in two high-coverage WGS datasets from 3552 Japanese individuals and 192 three-generation families (consisting of 1120 family members) in prospective genomic cohorts. The results showed that a considerable number of ROHs, especially short ones that may have remained undetected in conventionally used SNP-array data, can be detected in the WGS data. By filtering out sequencing errors and leveraging pedigree information, longer ROHs are more likely to be detected in WGS data than in SNP-array data. Additionally, we identified gene families within ROH islands that are associated with enriched pathways related to sensory perception of taste and odors, suggesting potential signatures of selection in these key genomic regions.</jats:p>

  10. Has the impact of cigarette smoking on mortality been underestimated by overlooking second-hand smoke? Tohoku medical megabank community-based cohort study 査読有り

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

    BMJ Public Health　2025年4月

    DOI： 10.1136/bmjph-2024-001746 　

    ISSN：2753-4294

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

  11. Risk factors and prediction for pediatric obesity: current status and future perspectives 査読有り

    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年4月

    DOI： 10.1507/endocrj.ej24-0724 　

    ISSN：0918-8959 1348-4540

  12. Reference-Based Standardization Approach Stabilizing Small Batch Risk Prediction via Polygenic Score. 国際誌 査読有り

    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年3月

    DOI： 10.1002/gepi.70002 　

    ISSN：0741-0395 1098-2272

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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.

  13. Degree of housing damage caused by the Great East Japan Earthquake and all-cause mortality in the community-based cohort study of the Tohoku Medical Megabank Project. 国際誌 査読有り

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

    Journal of epidemiology and community health　2025年1月15日

    DOI： 10.1136/jech-2024-223084 　

    ISSN：0143-005X 1470-2738

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

  14. Influence of physical activity on the epigenetic clock: evidence from a Japanese cross-sectional study. 国際誌 査読有り

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

    Clinical epigenetics　16　(1)　142-142　2024年10月15日

    DOI： 10.1186/s13148-024-01756-1 　

    ISSN：1868-7083

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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.

  15. Healthy lifestyle practice correlates with decreased obesity prevalence in individuals with high polygenic risk: TMM CommCohort study. 国際誌 査読有り

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

    Journal of human genetics　2024年8月22日

    DOI： 10.1038/s10038-024-01280-3 　

    ISSN：1434-5161 1435-232X

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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.

  16. 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年3月

    ISSN：1933-7191

    eISSN：1933-7205

  17. The Health History of First-Degree Relatives’ Dyslipidemia Can Affect Preferences and Intentions following the Return of Genomic Results for Monogenic Familial Hypercholesterolemia 査読有り

    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年3月

    DOI： 10.3390/genes15030384 　

  18. Relationship between traditional risk factors for hypertension and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study. 国際誌 査読有り

    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　2024年2月29日

    DOI： 10.1038/s41440-024-01582-1 　

    ISSN：0916-9636 1348-4214

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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.

  19. Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS) 査読有り

    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

    Journal of Epidemiology　2024年1月

    DOI： 10.2188/jea.je20230192 　

    ISSN：0917-5040 1349-9092

  20. Metabolomics profiles alterations in cigarette smokers and heated tobacco product users. 査読有り

    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年11月4日

    出版者・発行元： Japan Epidemiological Association

    DOI： 10.2188/jea.JE20230170 　

    ISSN：0917-5040 1349-9092

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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.

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

    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年9月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.ijcrp.2023.200216 　

    ISSN：2772-4875

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

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

    PLOS ONE　18　(8)　e0289029-e0289029　2023年8月9日

    出版者・発行元： Public Library of Science (PLoS)

    DOI： 10.1371/journal.pone.0289029 　

    ISSN：1932-6203

    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.

  23. Epigenetic profile of Japanese supercentenarians: a cross-sectional study 国際誌 査読有り

    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年2月1日

    出版者・発行元： Elsevier {BV}

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

    ISSN：2666-7568

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    BACKGROUND: Centenarians and supercentenarians with exceptional longevity are excellent models for research towards improvements of healthy life expectancy. Extensive research regarding the maintenance and reduction of epigenetic age has provided insights into increasing healthy longevity. To this end, we explored the epigenetic signatures reflecting hallmarks of exceptional healthy longevity, including avoidance of age-related diseases and cognitive functional decline. METHODS: In this cross-sectional study, we enrolled Japanese non-centenarians (eligible participants aged 20-80 years) from the Tohoku Medical Megabank Community-Based Cohort Study and centenarians and supercentenarians (aged 101-115 years) from the Tokyo Centenarian Study and the Japanese Semi-supercentenarian Study. We assessed participants' whole-blood DNA methylation profiles and then developed sex-specific and non-specific first-generation epigenetic clocks by elastic net regression, calculated individuals' epigenetic ages, and assessed their age acceleration. We also screened for age-related CpG sites in non-centenarians by epigenome-wide linear regression analyses and ANOVA. We subsequently investigated which CpG sites in centenarians and supercentenarians had DNA methylation patterns following the age-related findings obtained from non-centenarians and which did not. We further characterised CpG sites with hypermethylation or hypomethylation in the centenarians and supercentenarians using enrichment and protein-protein interaction network analyses. FINDINGS: We enrolled 421 non-centenarians (231 [55%] women and 190 [45%] men; age range 20-78 years), recruited between May 20, 2013, and March 31, 2016, and 94 centenarians and supercentenarians (66 women [70%] and 28 [30%] men; age range 101-115 years), recruited between Jan 20, 2001, and April 17, 2018. Non-sex-specific epigenetic clock showed the highest accuracy (r=0·96) based on which centenarians and supercentenarians had negative epigenetic age acceleration. Epigenome-wide association analyses further showed that centenarians and supercentenarians had younger-than-expected epigenetic states (DNA methylation profiles similar to those of non-centenarians) for 557 CpG sites enriched in cancer-related and neuropsychiatric-related genes, whereas these individuals had advanced (or older) epigenetic states for 163 CpG sites represented by genes related to TGF-β signalling, which is involved in anti-inflammatory responses and known to contribute to healthy ageing. INTERPRETATION: These results indicate that exceptionally healthy longevity depends not only on maintaining young epigenetic states but also on advanced states of specific epigenetic regions. FUNDING: The Japan Agency for Medical Research and Development, KDDI Research, and Keio University. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

  24. Association between plasma xanthine oxidoreductase activity and the renal function in a general Japanese population: The Tohoku Medical Megabank community-based cohort study. 国際誌 査読有り

    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年11月1日

    出版者・発行元： S. Karger {AG}

    DOI： 10.1159/000527654 　

    ISSN：1420-4096 1423-0143

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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.

  25. 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 査読有り

    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年10月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.ahjo.2022.100212 　

    ISSN：2666-6022

  26. Association between total type I collagen N-terminal propeptide and coronary artery disease risk score in the general Japanese population. 国際誌 査読有り

    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年8月

    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.

  27. Epigenome-wide Association Study Identified VTI1A DNA Methylation Associated with Accelerometer-assessed Physical Activity. 国際誌 査読有り

    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年6月11日

    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.

  28. Evaluation of short-term epigenetic age fluctuation 国際誌 査読有り

    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年6月

    出版者・発行元： 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.

  29. Potential DNA methylation biomarkers for the detection of clear cell renal cell carcinoma identified by a whole blood-based epigenome-wide association study 査読有り

    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年5月

    出版者・発行元： Springer Science and Business Media {LLC}

    DOI： 10.1186/s43682-022-00009-7 　

    ISSN：2730-7034

    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.

  30. Longitudinal DNA methylation dynamics as a practical indicator in clinical epigenetics. 国際誌 査読有り

    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年12月13日

    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.

  31. Low MICA gene expression confers an increased risk of Graves' disease: a Mendelian randomization study. 国際誌 査読有り

    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　2021年12月3日

    DOI： 10.1089/thy.2021.0417 　

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    BACKGROUND: Expression of 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 MHC 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 (MR) 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 (P = 4.2 × 10-3; OR per 1 S.D. difference in the expression: 0.983 [95% CI: 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 Graves' disease, 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.

  32. dbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project 国際誌 査読有り

    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, Masayuki Yamamoto, Michiaki Abe, Yayoi Aizawa, Yuichi Aoki, Koichi Chida, Inaho Danjoh, Shinichi Egawa, Ai Eto, Takamitsu Funayama, Nobuo Fuse, Yohei Hamanaka, Yuki Harada, Hiroaki Hashizume, Shinichi Higuchi, Sachiko Hirano, Takumi Hirata, Masahiro Hiratsuka, Atsushi Hozawa, Kazuhiko Igarashi, Jin Inoue, Noriko Ishida, Naoto Ishii, Tadashi Ishii, Mami Ishikuro, Kiyoshi Ito, Sadayoshi Ito, Maiko Kageyama, Fumiki Katsuoka, Hiroshi Kawame, Junko Kawashima, Masahiro Kikuya, Kengo Kinoshita, Kazuyuki Kitatani, Tomomi Kiyama, Hideyasu Kiyomoto, Tomoko Kobayashi, Eiichi Kodama, Mana Kogure, Kaname Kojima, Sachie Koreeda, Seizo Koshiba, Shihoko Koyama, Hisaaki Kudo, Kazuki Kumada, Shigeo Kure, Miho Kuriki, Shinichi Kuriyama, Yoko Kuroki, Norihide Maikusa, Satoshi Makino, Hiroko Matsubara, Hiroyuki Matsui, Hirohito Metoki, Takahiro Mimori, Naoko Minegishi, Kazuharu Misawa, Masako Miyashita, Satoshi Mizuno, Hozumi Motohashi, Ikuko N. Motoike, Satoshi Nagaie, Masato Nagai, Fuji Nagami, Masao Nagasaki, Sachiko Nagase, Naoki Nakamura, Tomohiro Nakamura, Naoki Nakaya, Keiko Nakayama, Akira Narita, Ichiko Nishijima, Takahiro Nobukuni, Kotaro Nochioka, Taku Obara, Soichi Ogishima, Noriaki Ohuchi, Gervais Olivier, Noriko Osumi, Hiroshi Otsu, Akihito Otsuki, Daisuke Saigusa, Sakae Saito, Tomo Saito, Masaki Sakaida, Mika Sakurai-Yageta, Yuki Sato, Yukuto Sato, Atsushi Sekiguchi, Chen-Yang Shen, Tomoko F. Shibata, Ritsuko Shimizu, Kazuro Shimokawa, Matsuyuki Shirota, Junichi Sugawara, Kichiya Suzuki, Yoichi Suzuki, Shu Tadaka, Makiko Taira, Takako Takai-Igarashi, Yuji Takano, Yasuyuki Taki, Gen Tamiya, Osamu Tanabe, Hiroshi Tanaka, Yukari Tanaka, Shunsuke Teraguchi, Takahiro Terakawa, Teiji Tominaga, Hiroaki Tomita, Akito Tsuboi, Naho Tsuchiya, Ichiro Tsuji, Masao Ueki, Akira Uruno, Nobuo Yaegashi, Junya Yamagishi, Yumi Yamaguchi-Kabata, Chizuru Yamanaka, Riu Yamashita, Jun Yasuda, Junji Yokozawa, Kazunori Waki, Makoto Sasaki, Junko Akai, Ryujin Endo, Akimune Fukushima, Ryohei Furukawa, Tsuyoshi Hachiya, Kouhei Hashizume, Jiro Hitomi, Yasushi Ishigaki, Shohei Komaki, Yuka Kotozaki, Takahiro Mikami, Motoyuki Nakamura, Naoyuki Nishiya, Satoshi Nishizuka, Yoko Nomura, Kuniaki Ogasawara, Hideki Ohmomo, Shinichi Omama, Ryo Otomo, Kotaro Otsuka, Kotaro Oyama, Kiyomi Sakata, Ryohei Sasaki, Mamoru Satoh, Namie Sato, Atsushi Shimizu, Yu Shiwa, Yoichi Sutoh, Nobuyuki Takanashi, Noriko Takebe, Fumitaka Tanaka, Ryoichi Tanaka, Kozo Tanno, Tomoharu Tokutomi, Kayono Yamamoto, Fumio Yamashita, Nobuo Fuse, Teiji Tominaga, Shigeo Kure, Nobuo Yaegashi, Kengo Kinoshita, Makoto Sasaki, Hiroshi Tanaka, Masayuki Yamamoto

    Human Genome Variation　8　(1)　44-44　2021年12月

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1038/s41439-021-00175-5 　

    eISSN：2054-345X

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    <title>Abstract</title>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.

  33. DNA methylation abnormalities and altered whole transcriptome profiles after switching from combustible tobacco smoking to heated tobacco products. 国際誌 査読有り

    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　2021年11月2日

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

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    BACKGROUND: The use of heated tobacco products (HTPs) 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 based on 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 were performed. RESULTS: Ten of the 17 genes were significantly hypomethylated in CS and HTP users compared to 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 to 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, since the molecular genetic effects of long-term HTP use are still unknown, long-term molecular epidemiological studies are needed. IMPACT: This study provides new insights into the molecular genetic effects on DNAm and transcriptome profiles in HTP users that switched from CS.

  34. 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. 国際誌 査読有り

    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年4月15日

    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.

  35. Plasma Xanthine Oxidoreductase Activity Is Associated with a High Risk of Cardiovascular Disease in a General Japanese Population. 国際誌 査読有り

    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)　2021年2月16日

    DOI： 10.3390/ijerph18041894 　

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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 < 0.001), diabetes (β = 0.09, p < 0.001), dyslipidemia (β = 0.08, p = 0.001), and uric acid (β = 0.13, p < 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.

  36. Evaluation of clinical formalin-fixed paraffin-embedded tissue quality for targeted-bisulfite sequencing. 国際誌 査読有り

    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年2月

    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.

  37. Weight Gain After 20 Years of Age is Associated with Unfavorable Lifestyle and Increased Prevalence of Metabolic Disorders. 国際誌 査読有り

    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年

    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.

  38. ALDH2 genotype modulates the association between alcohol consumption and AST/ALT ratio among middle-aged Japanese men: a genome-wide G × E interaction analysis. 国際誌 査読有り

    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年10月1日

    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.

  39. Epigenome-Wide Association Study Identifies a Novel DNA Methylation in Patients With Severe Aortic Valve Stenosis. 国際誌 査読有り

    Takahito Nasu, Mamoru Satoh, Hideki Ohmomo, Yuh Shiwa, Shohei Komaki, Kanako Ono, Atsushi Shimizu, Satoru Taguchi, Yuji Takahashi, Takuya Osaki, Yoshihiro Morino, Kenji Sobue, Makoto Sasaki

    Circulation. Genomic and precision medicine　13　(1)　e002649　2020年2月

    DOI： 10.1161/CIRCGEN.119.002649 　

  40. Study profile of The Tohoku Medical Megabank Community-Based Cohort Study. 査読有り

    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年1月11日

    DOI： 10.2188/jea.JE20190271 　

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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.

  41. Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project. 国際誌 査読有り

    Yuji Takahashi, Mamoru Satoh, Hideki Ohmomo, Fumitaka Tanaka, Takuya Osaki, Kozo Tanno, Takahito Nasu, Kiyomi Sakata, Yoshihiro Morino, Kenji Sobue, Makoto Sasaki

    Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals　24　(6)　566-573　2019年9月

    DOI： 10.1080/1354750X.2019.1606278 　

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    Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population. Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n = 30,193, age = 60.2 ± 11.5 year). Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90-3.89, p < 0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28-3.14, p < 0.001). Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.

  42. Plasma Xanthine Oxidoreductase Activity is Associated With Edothelial Dysfunction and Increased Arterial Stiffness in a General Japanese Population: the Iwate Tohoku Medical Megabank Project 査読有り

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

    CIRCULATION　139　2019年

    DOI： 10.1161/circ.139.suppl_1.P031 　

    ISSN：0009-7322

  43. Genome-wide analysis of polymorphism × sodium interaction effect on blood pressure identifies a novel 3′-BCL11B gene desert locus 国際誌 査読有り

    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年9月21日

    DOI： 10.1038/s41598-018-32074-1 　

  44. iMETHYL: an integrative database of human DNA methylation, gene expression, and genomic variation. 国際誌 査読有り

    Shohei Komaki, Yuh Shiwa, Ryohei Furukawa, Tsuyoshi Hachiya, Hideki Ohmomo, Ryo Otomo, Mamoru Satoh, Jiro Hitomi, Kenji Sobue, Makoto Sasaki, Atsushi Shimizu

    Human genome variation　5　(5)　18008-18008　2018年

    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.

  45. Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6–TMC8 and SIX3–SIX2 loci associated with HbA1c 国際誌 査読有り

    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)　16147-16147　2017年11月23日

    DOI： 10.1038/s41598-017-16493-0 　

    ISSN：2045-2322

  46. An epigenome-wide association study based on cell type-specific whole-genome bisulfite sequencing: Screening for DNA methylation signatures associated with bone mass 査読有り

    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年10月

    出版者・発行元：

    DOI： 10.15761/imm.1000307 　

    eISSN：2056-6360

  47. Genetic Predisposition to Ischemic Stroke: A Polygenic Risk Score. 国際誌 査読有り

    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年2月

    DOI： 10.1161/STROKEAHA.116.014506 　

    ISSN：0039-2499

    eISSN：1524-4628

  48. Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies. 国際誌 査読有り

    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　(1)　11-11　2017年

    DOI： 10.1038/s41525-017-0016-5 　

    ISSN：2056-7944

  49. Intraindividual dynamics of transcriptome and genome-wide stability of DNA methylation. 国際誌 査読有り

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

    Scientific reports　6　26424-26424　2016年5月19日

    DOI： 10.1038/srep26424 　

    ISSN：2045-2322

  50. Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols. 国際誌 査読有り

    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年

    DOI： 10.1371/journal.pone.0147519 　

    ISSN：1932-6203

  51. Presentation of noise during acute restraint stress attenuates expression of immediate early genes and arginine vasopressin in the hypothalamic paraventricular nucleus but not corticosterone secretion in rats. 国際誌 査読有り

    Koji Sugimoto, Hideki Ohmomo, Fumihiro Shutoh, Haruo Nogami, Setsuji Hisano

    Neuroscience research　96　20-9　2015年7月

    DOI： 10.1016/j.neures.2014.11.010 　

    ISSN：0168-0102

    eISSN：1872-8111

  52. Reduction of systematic bias in transcriptome data from human peripheral blood mononuclear cells for transportation and biobanking. 国際誌 査読有り

    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年

    DOI： 10.1371/journal.pone.0104283 　

    ISSN：1932-6203

  53. Spatiotemporal patterns of the Huntingtin-interacting protein 1-related gene in the mouse head. 国際誌 査読有り

    Tomoyuki Masuda, Chie Sakuma, Takayuki Ueno, Yuriko Yamada, Hideki Ohmomo, Shuichi Ueda, Toshiyuki Yamagishi, Hiroyuki Yaginuma

    Congenital anomalies　53　(4)　141-8　2013年12月

    DOI： 10.1111/cga.12023 　

    ISSN：0914-3505

    eISSN：1741-4520

  54. Property of Regenerating Serotonin Fibers in the Hippocampus of Human Migration Disorders Model

    Shuichi UEDA, Ayuka EHARA, Hideki OHMOMO

    Kansei Engineering International Journal　11　139-145　2012年

    出版者・発行元： Japan Society of Kansei Engineering

    DOI： 10.5057/kei.11.139 　

    ISSN：1884-0841 2185-7865

  55. Temporally distinct expression of vesicular glutamate transporters 1 and 2 during embryonic development of the rat olfactory system. 国際誌 査読有り

    Hideki Ohmomo, Ayuka Ehara, Sachine Yoshida, Fumihiro Shutoh, Shu-ichi Ueda, Setsuji Hisano

    Neuroscience research　70　(4)　376-82　2011年8月

    DOI： 10.1016/j.neures.2011.05.005 　

    ISSN：0168-0102

  56. 小胞性グルタミン酸トランスポーター

    久野節二, 伊奈鮎香, 吉田さちね, 大桃秀樹, 川野道宏

    生体の科学　61　(5)　400-401　2010年10月

    出版者・発行元： 医学書院

    ISSN：0370-9531

    eISSN：1883-5503

  57. POSTNATAL CHANGES IN EXPRESSION OF VESICULAR GLUTAMATE TRANSPORTERS IN THE MAIN OLFACTORY BULB OF THE RAT 査読有り

    H. Ohmomo, A. Ina, S. Yoshida, F. Shutoh, S. Ueda, S. Hisano

    NEUROSCIENCE　160　(2)　419-426　2009年5月

    DOI： 10.1016/j.neuroscience.2009.02.048 　

    ISSN：0306-4522

  58. Upregulated expression of neuropeptide Y in hypothalamic-pituitary system of rats by chronic dexamethasone administration. 国際誌 査読有り

    Jinko Konno, Sachine Yoshida, Ayuka Ina, Hideki Ohmomo, Fumihiro Shutoh, Haruo Nogami, Setsuji Hisano

    Neuroscience research　60　(3)　259-65　2008年3月

    DOI： 10.1016/j.neures.2007.11.005 　

    ISSN：0168-0102

    eISSN：1872-8111

  59. Cajal-Retzius cells and subplate neurons differentially express vesicular glutamate transporters 1 and 2 during development of mouse cortex. 国際誌 査読有り

    Ayuka Ina, Miki Sugiyama, Jinko Konno, Sachine Yoshida, Hideki Ohmomo, Haruo Nogami, Fumihiro Shutoh, Setsuji Hisano

    The European journal of neuroscience　26　(3)　615-23　2007年8月

    DOI： 10.1111/j.1460-9568.2007.05703.x 　

    ISSN：0953-816X

  60. The hypothalamic neuropeptide y neuron system of rats after long-term, high-dose dexamethasone treatment

    Konno, Jinko, Ina, Ayuka, Yoshida, Sachine, Ohmomo, Hideki, Shutoh, Fumihiro, Hisano, Setsuji

    NEUROSCIENCE RESEARCH　55　(Suppl. 1)　0-0　2006年1月

    出版者・発行元： ELSEVIER IRELAND LTD

    ISSN：0168-0102

  61. Changes in intensity of mRNA signals of a vesicular glutamate transporter (VGLUT) in the medial vestibular nucleus after microstimulation of the flocculus in mice

    Shutoh, Fumihiro, Ina, Ayuka, Yoshida, Sachine, Konno, Jinko, Ohmomo, Hideki, Nogami, Haruo, Hisano, SetsuJi

    NEUROSCIENCE RESEARCH　55　(Suppl. 1)　0-0　2006年1月

    出版者・発行元： ELSEVIER IRELAND LTD

    ISSN：0168-0102

  62. Identification of vesicular glutamate transporter (VGLUT) immunoreactivity in the early fetal mouse cortex

    Ina, Ayuka, Konno, Jinko, Yoshida, Sachine, Ohmomo, Hideki, Kawano, Hitoshi, Shutoh, Fumihiro, Nogami, Haruo, Hisano, Setsuji

    NEUROSCIENCE RESEARCH　55　(Suppl. 1)　0-0　2006年1月

    出版者・発行元： ELSEVIER IRELAND LTD

    ISSN：0168-0102

  63. Expression of vesicular glutamate transporter3 (VGLUT3) in the rat pineal gland

    Yoshida, Sachine, Ina, Ayuka, Konno, Jinko, Ohmomo, Hideki, Shutoh, Fumihiro, Nogami, Haruo, Hisano, Setsuji

    NEUROSCIENCE RESEARCH　55　(Suppl. 1)　0-0　2006年1月

    出版者・発行元： ELSEVIER IRELAND LTD

    ISSN：0168-0102

︎全件表示 ︎最初の5件までを表示

MISC 66

  1. Polygenic score for blood immunoglobulin E levels in adults explains food allergy risk in children

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

    JOURNAL OF IMMUNOLOGY　214　2025年11月

    DOI： 10.1093/jimmun/vkaf283.514 　

    ISSN： 0022-1767

    eISSN： 1550-6606

  2. 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年3月

    出版者・発行元： (一社)日本衛生学会

    ISSN： 0021-5082

    eISSN： 1882-6482

  3. 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(Web)　80　(Supplement)　2025年

    ISSN： 1882-6482

  4. 末梢血DNAメチル化と糖尿病との関連:エピゲノムワイド関連解析

    古川拓馬, 古川拓馬, 田中恵太郎, 西田裕一郎, 島ノ江千里, 大桃秀樹, 清水厚志, 原めぐみ

    日本疫学会学術総会講演集(Web)　35th　(Suppl.)　171-171　2025年

    出版者・発行元： (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  5. DNAメチル化解析および遺伝子発現解析を用いた加熱式たばこへの切り替えによる分子遺伝学的影響の解明

    大桃秀樹, 大桃秀樹, 原田成, 小巻翔平, 小巻翔平, 小野加奈子, 美辺詩織, 美辺詩織, 須藤洋一, 須藤洋一, 山崎弥生, 山崎弥生, 武林亨, 清水厚志, 清水厚志

    日本疫学会学術総会講演集(Web)　35th　(Suppl.)　171-171　2025年

    出版者・発行元： (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  6. エピゲノム年齢の回付による個別化予防の実現に向けたフィージビリティ・スタディ

    清水厚志, 清水厚志, 小巻翔平, 小巻翔平, 荒木重則, 美辺詩織, 美辺詩織, 山崎弥生, 山崎弥生, 須藤洋一, 須藤洋一, 大桃秀樹, 大桃秀樹

    日本遺伝カウンセリング学会誌　46　(2)　154-154　2025年

    出版者・発行元： (一社)日本遺伝カウンセリング学会

    ISSN： 1347-9628

  7. 喫煙歴と受動喫煙の組み合わせと総死亡の関連

    高瀬 雅仁, 中谷 直樹, 丹野 高三, 小暮 真奈, 畑中 里衣子, 中谷 久美, 千葉 一平, 時岡 紗由理, 永家 聖, 事崎 由佳, 大桃 秀樹, 田淵 貴大, 寳澤 篤

    日本公衆衛生学会総会抄録集　83回　265-265　2024年10月

    出版者・発行元： 日本公衆衛生学会

    ISSN： 1347-8060

  8. 独居と総死亡の関連 東北メディカル・メガバンク地域住民コホート調査

    事崎 由佳, 中谷 久美, 中谷 直樹, 小暮 真奈, 千葉 一平, 畑中 里衣子, 高瀬 雅仁, 時岡 紗由理, 永家 聖, 大桃 秀樹, 寶澤 篤, 丹野 高三

    日本公衆衛生学会総会抄録集　83回　362-362　2024年10月

    出版者・発行元： 日本公衆衛生学会

    ISSN： 1347-8060

  9. 独居・同居と婚姻状態の組み合わせと総死亡の関連 東北メディカル・メガバンク地域住民コホート調査

    事崎 由佳, 中谷 久美, 中谷 直樹, 小暮 真奈, 千葉 一平, 畑中 里衣子, 高瀬 雅仁, 時岡 紗由理, 永家 聖, 那須 崇人, 大桃 秀樹, 寳澤 篤, 丹野 高三

    東北公衆衛生学会誌　73rd (CD-ROM)　(73)　23-23　2024年7月

    出版者・発行元： 東北公衆衛生学会

    ISSN： 0915-549X

  10. 東北メディカル・メガバンク(TMM)計画におけるDNAメチル化解析によるDOHaD研究に向けた取り組み

    美辺 詩織, 小巻 翔平, 大桃 秀樹, 清水 厚志

    DOHaD研究　12　(1)　5-10　2024年6月

    出版者・発行元： (一社)日本DOHaD学会

    ISSN： 2187-2562

    eISSN： 2187-2597

  11. 多遺伝子スコア(PGS)が健康行動に与える影響を理解するためのコホート研究:研究プロファイル

    YOSHIDA Akiko, TOKUTOMI Tomoharu, TOYA Yukiko, FUKUSHIMA Akimune, OHMOMO Hideki, SUTOH Yoichi, KOTOZAKI Yuka, HACHIYA Tsuyoshi, SUZUMORI Nobuhiro, ISHIGAKI Yasushi, ASAHI Koichi, TANNO Kozo, SHIMIZU Atsushi, SASAKI Makoto

    日本人類遺伝学会大会(CD-ROM)　69th　2024年

  12. 精密医療における多遺伝子スコア算出のための堅牢なワークフローの開発

    SUTOH Yoichi, HACHIYA Tsuyoshi, OTSUKA-YAMASAKI Yayoi, TOKUTOMI Tomoharu, YOSHIDA Akiko, KOTOZAKI Yuka, KOMAKI Shohei, MINABE Shiori, OHMOMO Hideki, TANNO Kozo, FUKUSHIMA Akimune, SASAKI Makoto, SHIMIZU Atsushi

    日本人類遺伝学会大会(CD-ROM)　69th　2024年

  13. 大規模ゲノムコホートの踵骨定量的超音波測定T-score値を基盤とする多遺伝子スコアを用いた骨粗鬆症発症リスク予測モデルの構築

    山崎弥生, 須藤洋一, 八谷剛史, 小巻翔平, 美辺詩織, 大桃秀樹, 佐々木真理, 清水厚志

    日本骨粗鬆症学会雑誌　10　(Suppl.1 (CD-ROM))　486-486　2024年

    出版者・発行元： (一社)日本骨粗鬆症学会

    ISSN： 2189-8383

  14. 日本人集団における血中アミノ酸濃度のゲノムワイド関連解析(GWAS)とそれを用いた疾患との関連研究

    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, 松元美奈子, 宮川尚子, 枝川竣, 三宅温子, 須藤洋一, 大桃秀樹, 山崎弥生, 岡村智教, 清水厚志, 武林亨

    日本疫学会学術総会講演集(Web)　34th　(Suppl.)　99-99　2024年

    出版者・発行元： (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  15. エピゲノム年齢による個別化予防の実現に向けたフィージビリティ・スタディ

    清水厚志, 清水厚志, 清水厚志, 小巻翔平, 小巻翔平, 小巻翔平, 荒木重則, 荒木重則, 美辺詩織, 美辺詩織, 山崎弥生, 山崎弥生, 須藤洋一, 須藤洋一, 大桃秀樹, 大桃秀樹, 大桃秀樹

    日本遺伝カウンセリング学会誌　45　(2)　125-125　2024年

    出版者・発行元： (一社)日本遺伝カウンセリング学会

    ISSN： 1347-9628

  16. 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　176-176　2024年

    出版者・発行元： (一社)日本抗加齢医学会

  17. 東北メディカル・メガバンク(TMM)計画におけるDNAメチル化解析によるDOHaD研究に向けた取り組み

    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年

    DOI： 10.51067/dohad.12.1_5 　

    ISSN： 2187-2597

  18. 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年11月

    出版者・発行元： (一社)日本肥満学会

    ISSN： 1343-229X

  19. 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年8月

    出版者・発行元： (一社)日本DOHaD学会

    ISSN： 2187-2562

    eISSN： 2187-2597

  20. 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年6月

    出版者・発行元： (一社)日本動脈硬化学会

    ISSN： 1347-7099

  21. 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年6月

    出版者・発行元： (一社)日本抗加齢医学会

  22. 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年6月

    出版者・発行元： (一社)日本抗加齢医学会

  23. 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年6月

    出版者・発行元： (一社)日本抗加齢医学会

  24. 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年3月

    出版者・発行元： (一社)日本衛生学会

    ISSN： 0021-5082

    eISSN： 1882-6482

  25. 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年3月

    出版者・発行元： (一社)日本衛生学会

    ISSN： 0021-5082

    eISSN： 1882-6482

  26. 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年

    ISSN： 1882-6482

  27. 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年

    ISSN： 2187-2597

  28. 霊長類の脳が有機ヒ素によって変性する際の分子機序の解明

    増田知之, 大桃秀樹, 文東美紀, 仲地ゆたか, 岩本和也

    日本組織細胞化学会総会・学術集会講演プログラム・予稿集　64th (CD-ROM)　30-30　2023年

    出版者・発行元： 日本組織細胞化学会

  29. 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

    大桃秀樹, 新井恵吏, 吉田輝彦, 金井弥栄, 清水厚志

    日本癌学会学術総会抄録集(Web)　81回　P-1088　2022年9月

    出版者・発行元： (一社)日本癌学会

    ISSN： 0546-0476

  30. 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年4月

    出版者・発行元： (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  31. 男性の飲酒量とAST/ALT比の関連を修飾するALDH2遺伝子多型の交互作用効果

    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年

  32. 淡明細胞型腎細胞がん(ccRCC)に対するDNAメチル化バイオマーカー候補の同定

    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年

  33. 臨床応用に向かう疾患メタボロミクスの最前線 オミックス解析における品質管理の重要性 いわて東北メディカル・メガバンクにおける取り組み

    大桃 秀樹

    日本臨床検査医学会誌　69　(10)　785-785　2021年10月

    出版者・発行元： (一社)日本臨床検査医学会

    ISSN： 2436-2727

  34. 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年1月

    出版者・発行元： (一社)日本疫学会

    ISSN： 0917-5040

    eISSN： 1349-9092

  35. 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年11月

    出版者・発行元： (一社)日本糖尿病合併症学会

  36. 臨床応用に向かう疾患メタボロミクスの最前線 オミックス解析における品質管理の重要性 いわて東北メディカル・メガバンクにおける取り組み

    大桃 秀樹

    臨床病理　68　(補冊)　076-076　2020年10月

    出版者・発行元： (一社)日本臨床検査医学会

    ISSN： 0047-1860

  37. 腹囲が生活習慣病に及ぼす影響の肥満者と非肥満者における違いの検討

    武部 典子, 丹野 高三, 長谷川 豊, 大桃 秀樹, 佐々木 亮平, 高梨 信之, 坂田 清美, 平田 匠, 寶澤 篤, 佐々木 真理, 石垣 泰

    糖尿病　63　(Suppl.1)　S-134　2020年8月

    出版者・発行元： (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  38. 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年

  39. 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年11月

    ISSN： 0009-7322

    eISSN： 1524-4539

  40. 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年7月

    出版者・発行元： 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  41. 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年7月

    出版者・発行元： 日本遺伝カウンセリング学会

    ISSN： 1347-9628

  42. 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年4月

    出版者・発行元： (一社)日本内分泌学会

    ISSN： 0029-0661

    eISSN： 2186-506X

  43. 成人後の体重増加と生活習慣関連因子および生活習慣病との関連

    武部 典子, 丹野 高三, 大桃 秀樹, 佐藤 衛, 坂田 清美, 平田 匠, 寳澤 篤, 佐々木 真理, 石垣 泰

    糖尿病　62　(Suppl.1)　S-286　2019年4月

    出版者・発行元： (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  44. 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年4月

    出版者・発行元： (一社)日本内分泌学会

    ISSN： 0029-0661

  45. 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年1月30日

  46. 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年

  47. 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年10月5日

    出版者・発行元： バイオサイエンスデータベースセンター

    DOI： 10.18908/togo2018.p048 　

  48. 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年4月

    出版者・発行元： (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  49. 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年4月

    出版者・発行元： (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  50. 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年12月

    ISSN： 1059-1524

    eISSN： 1939-4586

  51. 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

    清水厚志, 八谷剛史, 大桃秀樹, 志波優, 古川亮平

    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年

  52. 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

    大桃秀樹, 八谷剛史, 志波優, 古川亮平, 小野加奈子, 伊藤薫樹, 石田陽治, 佐藤衛, 人見次郎, 祖父江憲治, 清水厚志

    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年

  53. 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

    志波優, 古川亮平, 大桃秀樹, 小野加奈子, 佐藤衛, 人見次郎, 祖父江憲治, 八谷剛史, 清水厚志

    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年

  54. 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

    清水厚志, 八谷剛史, 丹野高三, 福島明宗, 志波優, 大桃秀樹, 古川亮平, 山本佳世乃, 小野加奈子, 佐藤衛, 佐藤衛, 人見次郎, 祖父江憲治

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

  55. モノアミンの変調による異常攻撃行動を起こす動物モデルの作製

    上田 秀一, 大桃 秀樹, 江原 鮎香, 増田 知之, 中舘 和彦

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集　22回・42回　166-166　2012年10月

    出版者・発行元： 日本臨床精神神経薬理学会・日本神経精神薬理学会

  56. Zitter ratの加齢に伴うてんかん感受性の増大および海馬の構造変化

    大桃 秀樹, 江原 鮎香, 増田 知之, 上田 秀一

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集　22回・42回　191-191　2012年10月

    出版者・発行元： 日本臨床精神神経薬理学会・日本神経精神薬理学会

  57. げっ歯類脳神経核におけるattractin分布の解析

    中舘 和彦, 榊原 伸一, 大桃 秀樹, 江原 鮎香, 上田 秀一

    解剖学雑誌　85　(Suppl.)　190-190　2010年3月

    出版者・発行元： (一社)日本解剖学会

    ISSN： 0022-7722

  58. 選択的神経毒の新生仔期髄液内投与後における再生セロトニン線維の特性

    上田 秀一, 江原 鮎香, 大桃 秀樹, 中舘 和彦, 榊原 伸一, 吉本 寛司

    日本組織細胞化学会総会・学術集会講演プログラム・予稿集　50回　86-86　2009年9月

    出版者・発行元： 日本組織細胞化学会

  59. Zitterラットの進行性黒質ドーパミン神経変性におけるミクログリアの関与

    中舘 和彦, 大桃 秀樹, 江原 鮎香, 榊原 伸一, 上田 秀一

    日本組織細胞化学会総会・学術集会講演プログラム・予稿集　50回　87-87　2009年9月

    出版者・発行元： 日本組織細胞化学会

  60. ラット主嗅球における小胞性グルタミン酸輸送体1(VGLUT1)とVGLUT2の発達

    大桃 秀樹, 江原 鮎香, 中舘 和彦, 久野 節二, 上田 秀一

    解剖学雑誌　84　(2)　54-54　2009年6月

    出版者・発行元： (一社)日本解剖学会

    ISSN： 0022-7722

  61. 進行性神経変性疾患モデル動物(Zitterラット)黒質におけるミクログリアの解析

    中舘 和彦, 門脇 太郎, 中村 新, 榊原 伸一, 大桃 秀樹, 江原 鮎香, 上田 秀一

    解剖学雑誌　84　(Suppl.)　185-185　2009年3月

    出版者・発行元： (一社)日本解剖学会

    ISSN： 0022-7722

  62. ラット主嗅球における小胞性グルタミン酸輸送体の発達変化

    大桃 秀樹, 江原 鮎香, 中舘 和彦, 榊原 伸一, 久野 節二, 上田 秀一

    解剖学雑誌　84　(Suppl.)　187-187　2009年3月

    出版者・発行元： (一社)日本解剖学会

    ISSN： 0022-7722

  63. 進行性神経変性に関与するMahogunin Ring Finger 1(Mgrn1)のラット中枢神経系における分布解析

    中舘 和彦, 榊原 伸一, 大桃 秀樹, 江原 鮎香, 上田 秀一

    日本組織細胞化学会総会・学術集会講演プログラム・予稿集　49回　60-60　2008年10月

    出版者・発行元： 日本組織細胞化学会

  64. ラット視床下部、正中隆起におけるAttractin発現様式 Zitterラットとの比較

    中舘 和彦, 榊原 伸一, 大桃 秀樹, 上田 秀一

    解剖学雑誌　83　(Suppl.)　246-246　2008年3月

    出版者・発行元： (一社)日本解剖学会

    ISSN： 0022-7722

  65. Zitterラットの遅発性ドーパミン細胞変性とミクログリア変化

    上田 秀一, 大桃 秀樹, 中舘 和彦, 榊原 伸一

    解剖学雑誌　83　(Suppl.)　250-250　2008年3月

    出版者・発行元： (一社)日本解剖学会

    ISSN： 0022-7722

  66. 中枢神経系前駆細胞における新規遺伝子Radmisの発現

    榊原 伸一, 中舘 和彦, 大桃 秀樹, 小川 哲郎, 上田 秀一

    解剖学雑誌　82　(Suppl.)　210-210　2007年3月

    出版者・発行元： (一社)日本解剖学会

    ISSN： 0022-7722

︎全件表示 ︎最初の5件までを表示

書籍等出版物 3

  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年8月

    ISBN: 9784815730529

  2. 実験医学別冊：NGSアプリケーション RNA-Seq実験ハンドブック

    大桃 秀樹, 古川 亮平, 清水 厚志

    羊土社　2016年3月

    ISBN: 9784758101943

  3. 次世代シークエンサーDRY解析教本

    大桃 秀樹

    学研メディカル秀潤社　2015年10月

    ISBN: 9784780909203

講演・口頭発表等 6

  1. 低インプットDNAメチル化解析手法の確立と Avida Methyl Reagent Kitによる新たな可能性 招待有り

    美辺詩織, 大桃秀樹, 清水厚志

    第18回日本エピジェネティクス研究会年会　2025年6月19日

  2. バイオバンク利用研究の最前線 招待有り

    大桃秀樹

    MDB利用促進特別セミナー　2024年12月3日

  3. TMM計画で公開するデータベースの利活用とデータ分譲について 招待有り

    大桃秀樹

    第８回ゲノムコホート研究における遺伝統計学セミナー　2023年8月25日

  4. ゲノム・オミックス解析

    大桃秀樹

    筑波大学大学院神経科学先端セミナー　2023年2月3日

  5. 次世代シークエンサーDRY解析教本による遺伝子発現解析 招待有り

    大桃秀樹

    AJACSa三島2　2016年2月25日

  6. 遠隔地から輸送された血液細胞を用いたトランスクリプトーム解析 招待有り

    大桃秀樹

    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年2月6日

︎全件表示 ︎最初の5件までを表示

産業財産権 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

    産業財産権の種類: 特許権

  2. 環境因子、中間形質または疾患と関連性のあるCpG部位の候補となるCpG部位を特定する方法

    八谷 剛史, 清水 厚志, 古川 亮平, 志波 優, 大桃 秀樹

    産業財産権の種類: 特許権

共同研究・競争的資金等の研究課題 13

  1. NCDs・フレイル予防の共通経路としての代謝物バイオマーカーの有用性評価と検証

    武林 亨, 寳澤 篤, 平山 明由, 宮川 尚子, 清水 厚志, 三浦 克之, 大桃 秀樹, 小巻 翔平

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (A)

    研究機関：Keio University

    2023年4月1日 ～ 2028年3月31日

  2. 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 競争的資金

    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

    2025年4月 ～ 2028年3月

  3. 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

    2025年4月 ～ 2028年3月

  4. 淡明細胞型腎細胞がんに対するDNAメチル化バイオマーカーの実用化に向けた検討

    大桃 秀樹, 小巻 翔平

    2025年4月 ～ 2028年3月

  5. 臍帯血ゲノム・エピゲノムによる小児肥満複合リスク予測モデルの開発と検証

    清水 厚志, 土屋 賢治, 須藤 洋一, 栗山 進一, 大桃 秀樹

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (B)

    研究機関：Iwate Medical University

    2023年4月1日 ～ 2026年3月31日

  6. 慢性腎臓病発症・進展の先天的残余リスクに関する遺伝統計学的検討

    吉川 和寛, 大桃 秀樹, 旭 浩一

    2023年4月1日 ～ 2026年3月31日

  7. 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

    2022年4月1日 ～ 2026年3月31日

  8. 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, 八木 淳子, 真柳 平, 福本 健太郎, 清水 厚志, 大桃 秀樹, 小巻 翔平

    2021年4月1日 ～ 2024年3月31日

  9. 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

    2020年4月1日 ～ 2023年3月31日

    詳細を見る 詳細を閉じる

    2021年度の計画では、国内のブレインバンクからアルツハイマー病（AD）患者の全血DNA・脳組織・遺伝子多型情報の分譲を受け、CDMV-seq（common DNA methylation variation sequencing）を実施し、AD患者に特異的なDNAメチル化バイオマーカーの探索を予定していた。 当該ブレインバンクからAD患者の試料と情報の分譲を受けるため、ブレインバンク担当者と複数回やりとりした結果、研究計画書追加の修正と倫理審査承認を要請され、研究計画書・承認済倫理審査申請書の改訂を行なった。倫理委員会承認後に、ブレインバンクに再度分譲申請を行ったところ、同担当者より全血由来DNAの分譲には、別途バイオバンクジャパン（BBJ）への申請が必要との指摘があり、改めてBBJ事務局への問い合わせと試料・情報利用の申請準備を進め、申請を行った。 上記と並行して、最新のAD感受性多型について文献ならびに公開データを調査し、変異解析の対象とする一塩基多型（SNP）リストを作成した。これらの変異解析は検査会社に委託する予定であったが、一部のSNPの解析が検査会社では実施困難であることが判明したため、本研究班で解析するための独自の条件検討を行い、解析準備を行った。 また、当初予定していた東北メディカル・メガバンク（TMM）計画参加者へのアドオンリクルートについては、DNAメチル化バイオマーカーの同定に至っていない現状で実施することは困難と判断し、2022年度の計画の見直しを行った。

  10. サルコメア蛋白遺伝子のエピゲノム異常に着目した拡張型心筋症の病因解明

    佐藤 衛, 大桃 秀樹

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    研究種目：Grant-in-Aid for Scientific Research (C)

    研究機関：Iwate Medical University

    2019年4月1日 ～ 2022年3月31日

    詳細を見る 詳細を閉じる

    拡張型心筋症（DCM）は、難治性心筋疾患の一つである。特に、若年発症例は、生命予後が極めて悪く、その発症メカニズムの解明は急務である。本研究では、DCMでのサルコメア蛋白遺伝子群の後天的遺伝子制御異常としてエピジェネティクス異常に着目し、以下の3つの項目を目的として挙げる。 1) DCM群および対照群から採取した心筋生検組織を対象とし、サルコメア蛋白遺伝子群をコードするCpGサイトのDNAメチル化解析を行い、DCMに特異的なDNAメチル化部位を同定する。 2) 上記のサルコメア蛋白遺伝子のトランスクプトーム制御する microRNA 発現異常について解析を行い、DNA メチル化との関連解析を行いDCMの発症のメカニズムを探求する。3) 病態の進行および生命予後に関連するエピジェネティクス制御異常を探索する。 本年度は、症例のリクルートおよび心筋生検サンプルの収集を行い、さらに、DNAメチル化解析およびmicroRNA解析のための研究方法の確立を目指した。孤発性DCMでのサルコメア蛋白遺伝子のエピジェネティクス異常の解析のために、対象をdiscovery group、replication groupおよびcontrol groupに分類し、症例のリクルートおよびサンプル収集を行った。 さらに、本実験の方法論の確立のために、研究への参加の同意を得た大動脈弁狭窄症(AS)群および対照群を対象とし、末梢血単核細胞(PBMCs)での次世代シーケンサー（NGS）を用いたエピゲノムワイド関連解析(EWAS)を実施し候補DNAメチル化部位を同定し、PyroMark システムにより検証した(Nasu T, et al. Circ Genom Precis Med. 2020;13:e002649)。

  11. 強度別身体活動と末梢血DNAメチル化および結腸癌・乳癌リスクに関するコホート研究

    田中 恵太郎, 原 めぐみ, 西田 裕一郎, 大桃 秀樹, 島ノ江 千里

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    研究種目：Grant-in-Aid for Scientific Research (A)

    研究機関：Saga University

    2017年4月1日 ～ 2020年3月31日

    詳細を見る 詳細を閉じる

    佐賀市民約1万2千人のコホート研究に基づいて、加速度計で計測した身体活動と関連する末梢血DNAメチル化（約44万ヶ所）を網羅的に探索した。また、身体活動と結腸癌・乳癌の関連を検討し、その関連にDNAメチル化が介在しているかを検討した。網羅的探索でcg07030336（VTI1A・ZDHHC6遺伝子）が身体活動と有意な正の関連を示し、このメチル化は血中CRP・サイトカインと多彩な相関を示した。身体活動と結腸癌の関連は見られなかったが、高強度身体活動（6メッツ以上）と乳癌の有意な負の関連が示された。しかし、cg07030336は結腸癌・乳癌と有意な関連を示さず、上記の介在的役割は示されなかった。

  12. 身体活動と末梢血DNAメチル化、炎症マーカーおよび生活習慣病リスクのコホート研究

    田中 恵太郎, 原 めぐみ, 西田 裕一郎, 島ノ江 千里, 大桃 秀樹, 桧垣 靖樹

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    研究種目：Grant-in-Aid for Scientific Research (B)

    研究機関：Saga University

    2014年4月1日 ～ 2017年3月31日

    詳細を見る 詳細を閉じる

    佐賀市民約1万2千人のコホート研究に基づいて、加速度計で計測した身体活動量と末梢血ASC遺伝子メチル化の関連を検討した。また、身体活動と脳梗塞の関連を検討し、その関連にASC遺伝子メチル化が介在しているかを検討した。横断研究と縦断研究では、身体活動量とASC遺伝子メチル化の間に正の関連が見られ、特に低強度の身体活動量が強く影響していた。またASC遺伝子メチル化は血中炎症マーカーと負の関連を示した。症例コホート研究による身体活動と脳梗塞の関連は明らかでなく、ASC遺伝子メチル化の介在は観察されなかった。身体活動がASC遺伝子メチル化に影響を与え、さらに全身性炎症に影響を及ぼす可能性が示唆された。

  13. 中枢神経系幹細胞特異的遺伝子の機能解析

    中舘 和彦, 大桃 秀樹, 榊原 伸一

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    研究種目：Grant-in-Aid for Scientific Research (C)

    研究機関：Dokkyo Medical University

    2008年 ～ 2010年

    詳細を見る 詳細を閉じる

    我々が既に単離同定している神経幹細胞に発現する新規遺伝子群のなかかのひとつSE90/radmis遺伝子について解析を進めた。in situ hybridization解析により、radmis mRNA発現は胎生期の脳室周囲層、および生後や成体脳の側脳室の脳室下層といった神経幹細胞が局在すると考えられる部位での発現が認められた。また特異的抗体による組織学的解析の結果、radmisタンパクは神経幹細胞の放射状細胞突起と分裂期紡錘体微小管に一過性に局在し、分裂後は速やかに後期促進複合体APC/Cdh1によるユビキチン化を受けてタンパクが分解され、幹細胞内から除去される可能性が示された。実際の個体レベルでの神経発生過程でのradmis遺伝子の機能を検討するため、ユビキチン化を受けないよう改変した変異型radmis遺伝子を作製し、子宮内電気穿孔法によりマウス胎児の脳室内へ遺伝子導入を行った。その結果、radmis遺伝子を強制発現した神経幹細胞では分裂の亢進と細胞移動の異常が起きる事が明らかとなった。以上のデータからradmisが神経幹細胞の分裂制御に重要な働きを持つことが示唆された。

︎全件表示 ︎最初の5件までを表示