Epigenome-wide association studies for common human diseases related with mental stress

• Project/Area Number: 18K10049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: Saga University
• Principal Investigator: Shimanoe Chisato 佐賀大学, 医学部, 教授 (10734064)
• Co-Investigator(Kenkyū-buntansha): 松本 明子 佐賀大学, 医学部, 准教授 (10330979) ; 田中 恵太郎 佐賀大学, 医学部, 教授 (50217022) ; 西田 裕一郎 佐賀大学, 医学部, 講師 (50530185) ; 原 めぐみ 佐賀大学, 医学部, 准教授 (90336115)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 網羅的エピゲノムワイド関連解析 / 11βHSD / 精神ストレス / HbA1c / コホート研究 / ストレス対処行動 / DNAメチル化 / エピゲノムワイド関連解析 / 糖尿病 / コーホート研究 / CYP11B1 / Metylation / 心理ストレス / コルチゾール / コルチゾン / メタボリックシンドローム / 自覚ストレス / 抑うつ / プロスタグランジンE2 / グルココルチコイド活性 / LC-MSMS / DNA メチル化 / 生活習慣病

Outline of Final Research Achievements

Using data from a Japan Multi-institutional Collaborative Cohort study, Genome-Wide Association Studies (GWAS), Epigenome-Wide Association Studies (EWAS), and biomarkers discovery research aimed at elucidating the mechanisms involved in mental and physical health were performed. As a result, gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression. However, we could not detect DNA methylation sites significantly associated with mental stress and five coping behaviors. On the other hand, we found a relationship between the biomarker that reflects the activity of 11βHSD and mental stress, and some methylation sites associated with HbA1c levels among the methylation of six CpG islands of CYP11B1 were detected.

Academic Significance and Societal Importance of the Research Achievements

精神健康と身体的疾患の関連メカニズムについてのエビデンスは不十分なままである。GWASやEWASにより、精神ストレスに関与する新たな遺伝子多型やDNAのメチル化部位を検討することは、これまで未解明であった精神ストレスが疾患発症につながるメカニズムに寄与するエビデンスを提供できる。本研究で示唆された感情表出に関連する新規の遺伝子多型、精神ストレスと関連する新規マーカー、本バイオマーカーに関連するメチル化部位のHbA1cのレベルとの関連は、次世代の個別化医療に資するモニタリングマーカーの開発、予防対策、創薬の開発につなげることが期待できる。

Research Products

• [Journal Article] Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c: population-based cross-sectional and longitudinal studies. (2022)
  • Author(s): Furukawa T, Nishida Y, Hara M, et al.
  • Journal Title: BMJ Open Diabetes Res Care. Volume: 10 Issue: 1 Pages: e002479-e002479
  • DOI: 10.1136/bmjdrc-2021-002479
  • Peer Reviewed / Open Access
• [Journal Article] Association of perceived stress and coping strategies with the renal function in middle-aged and older Japanese men and women. (2022)
  • Author(s): Koga K, Hara M, Shimanoe C, Nishida Y, Furukawa T, Iwasaka C, Tanaka K, Otonari J, Ikezaki H, Kubo Y, Kato Y, Tamura T, Hishida A, Matsuo K, Ito H, Nakamura Y, Kusakabe M, Nishimoto D, Shibuya K, Suzuki S, Watanabe M, Ozaki E, Matsui D, Kuriki K, Takashima N, Kadota A, Arisawa K, Katsuura-Kamano S, Takeuchi K, Wakai K.
  • Journal Title: Sci Rep. Volume: 12 Issue: 1 Pages: 291-291
  • DOI: 10.1038/s41598-021-04324-2
  • Peer Reviewed / Open Access
• [Journal Article] Epigenome-Wide Association Study Identified VTI1A DNA Methylation Associated With Accelerometer-Assessed Physical Activity (2022)
  • Author(s): NISHIDA YUICHIRO、HARA MEGUMI、OHMOMO HIDEKI、ONO KANAKO、SHIMIZU ATSUSHI、HORITA MIKAKO、SHIMANOE CHISATO、TAGUCHI NAOTO、HIGAKI YASUKI、TANAKA KEITARO
  • Journal Title: Medicine & Science in Sports & Exercise Volume: 54 Issue: 11 Pages: 1879-1888
  • DOI: 10.1249/mss.0000000000002970
  • Peer Reviewed
• [Journal Article] Development of an enzyme-linked immunosorbent assay for the quantification of O-Phosphoethanolamine in human plasma (2022)
  • Author(s): Tetsuya Saita, Hiroto Kataoka, Rintaro Sogawa, Tadashi Hayama, Ryoko Tomita, Akira Monji, Yoshito Mizoguchi, Chisato Shimanoe
  • Journal Title: Analytical Biochemistry Volume: 659 Pages: 114952-114952
  • DOI: 10.1016/j.ab.2022.114952
  • Peer Reviewed / Open Access
• [Journal Article] Associations of breastfeeding history with metabolic syndrome and cardiovascular risk factors in community-dwelling parous women: The Japan Multi-Institutional Collaborative Cohort Study (2022)
  • Author(s): Matsunaga, T., Kadomatsu, Y., Tsukamoto, M., ...Takeuchi, K., Wakai, K.
  • Journal Title: PLoS ONE Volume: 17 Issue: 1 Pages: e0262252-e0262252
  • DOI: 10.1371/journal.pone.0262252
  • Peer Reviewed / Open Access
• [Journal Article] Association of skipping breakfast and short sleep duration with the prevalence of metabolic syndrome in the general Japanese population: Baseline data from the Japan Multi-Institutional Collaborative cohort study (2021)
  • Author(s): Katsuura-Kamano, S., Arisawa, K., Uemura, H., ...Takeuchi, K., Wakai, K.
  • Journal Title: Preventive Medicine Reports Volume: 24 Pages: 101613-101613
  • DOI: 10.1016/j.pmedr.2021.101613
  • Peer Reviewed / Open Access
• [Journal Article] Association between habitual coffee consumption and skeletal muscle mass in middle‐aged and older Japanese people (2021)
  • Author(s): Iwasaka Chiharu、Yamada Yosuke、Nishida Yuichiro、Hara Megumi、Yasukata Jun、Miyoshi Nobuyuki、Shimanoe Chisato、Nanri Hinako、Furukawa Takuma、Koga Kayoko、Horita Mikako、Higaki Yasuki、Tanaka Keitaro
  • Journal Title: Geriatrics & Gerontology International Volume: 21 Issue: 10 Pages: 950-958
  • DOI: 10.1111/ggi.14264
  • Peer Reviewed / Open Access
• [Journal Article] Perceived stress, depressive symptoms, and cortisol-to-cortisone ratio in spot urine in 6878 older adults (2021)
  • Author(s): Shimanoe, C., Matsumoto A., Hara, M., Akao C., Nishida, Y., Horita, M.,Nanri H., Higaki, Y., Tanaka, K
  • Journal Title: Psychoneuroendocrinology Volume: 125 Pages: 105125-105125
  • DOI: 10.1016/j.psyneuen.2020.105125
  • Peer Reviewed / Open Access
• [Journal Article] Sedentary Time is Associated with Cardiometabolic Diseases in A Large Japanese Population: A Cross-Sectional Study (2020)
  • Author(s): Koyama, T., Kuriyama, N., Ozaki, E., Tomida, S., Uehara, R., Nishida, Y., Shimanoe, C., et al.,
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 27 Issue: 10 Pages: 1097-1107
  • DOI: 10.5551/jat.54320
  • NAID: 130007920604
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2020-10-01
  • Peer Reviewed / Open Access
• [Journal Article] A genome-wide association study in Japanese identified one variant associated with a preference for a Japanese dietary pattern (2020)
  • Author(s): Suzuki Harumitsu、Nakamura Yasuyuki、Matsuo Keitaro、Imaeda Nahomi、Goto Chiho、Wakai Kenji et al.
  • Journal Title: European Journal of Clinical Nutrition Volume: - Issue: 6 Pages: 937-945
  • DOI: 10.1038/s41430-020-00823-z
  • Peer Reviewed
• [Journal Article] Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients. (2020)
  • Author(s): Nakayama A, Takada T, et al.
  • Journal Title: Ann Rheum Dis. Volume: 79 Issue: 5 Pages: 657665-657665
  • DOI: 10.1136/annrheumdis-2019-216644
  • NAID: 120007042436
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between alcohol intake pattern and metabolic syndrome components and simulated change by alcohol intake reduction: A cross-sectional study from the Japan Multi-Institutional Collaborative Cohort Study (2020)
  • Author(s): Shimoshikiryo, I., Ibusuki, R., Shimatani, K., Nishimoto, D., Takezaki, T., Nishida, Y., Shimanoe, C., Hishida, A., Tamura, T., Okada, R., Kubo, Y., Ozaki, E., Matsui, D., Suzuki, S., Nakagawa-Senda, H., Kuriki, K., Kita, Y., Takashima, N., et al and J-MICC Study Group
  • Journal Title: Alcohol Volume: 89 Pages: 129-138
  • DOI: 10.1016/j.alcohol.2020.09.002
• [Journal Article] Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals (2019)
  • Author(s): Nakatochi M, Kanai M, Nakayama A, Hishida A, Kawamura Y, Ichihara S, Akiyama M, Ikezaki H, Furusyo N, Shimizu S, Yamamoto K, et al.
  • Journal Title: Commun Biol. Volume: 2 Issue: 1 Pages: 115-115
  • DOI: 10.1038/s42003-019-0339-0
  • NAID: 120006937615
  • URL: https://pure.teikyo.jp/en/publications/d2b1a87f-6b8d-4bb5-a753-843e5cd6647d
  • Peer Reviewed / Open Access
• [Journal Article] Association of genetic risk score and chronic kidney disease in a Japanese population (2019)
  • Author(s): Fujii R, Hishida A, Nakatochi M, Furusyo N, Murata M, Tanaka K, Shimanoe C, Suzuki S, Watanabe M, Kuriyama N, Koyama T, Takezaki T, Shimoshikiryo I, Arisawa K, Katsuura-Kamano S, Takashima N, Turin TC, Kuriki K, Endoh K, Mikami H, Nakamura Y, Oze I, Ito H, Kubo M, Momozawa Y, Kondo T, Naito M, Wakai K
  • Journal Title: Nephrology Volume: 印刷中 Issue: 6 Pages: 670-673
  • DOI: 10.1111/nep.13479
  • Peer Reviewed
• [Journal Article] Independent relationships of daily life activity and leisure-time exercise with metabolic syndrome and its traits in the general Japanese population (2019)
  • Author(s): Hirokazu Uemura, Sakurako Katsuura-Kamano, Yuki Iwasaki, Kokichi Arisawa, Asahi Hishida, Rieko Okada, et al.
  • Journal Title: Endocrine Volume: 印刷中 Issue: 3 Pages: 552-563
  • DOI: 10.1007/s12020-019-01926-9
  • Peer Reviewed / Open Access
• [Journal Article] Habitual Light-intensity Physical Activity and ASC Methylation in a Middle-aged Population (2019)
  • Author(s): Nishida Y、Hara M、Higaki Y、Taguchi N、Nakamura K、Nanri H、Horita M、Shimanoe C、Yasukata J、Miyoshi N、Yamada Y、Higashimoto K、Soejima H、Tanaka K
  • Journal Title: International Journal of Sports Medicine Volume: 40 Issue: 10 Pages: 670-677
  • DOI: 10.1055/a-0965-1374
  • Peer Reviewed
• [Journal Article] A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression (2018)
  • Author(s): Shimanoe C, Hachiya T, Hara M, Nishida Y, Tanaka K, Sutoh Y, Shimizu A, et al
  • Journal Title: Genes, Brain and Behavior Volume: 印刷中 Issue: 2
  • DOI: 10.1111/gbb.12481
  • Peer Reviewed
• [Presentation] ミトコンドリアハプログループと糖尿病罹患の関連および身体活動の影響 (2022)
  • Author(s): 古川 拓馬, 西田 裕一郎, 原 めぐみ, 島ノ江 千里, 古賀 佳代子, 岩坂 知治, 福 典之, 檜垣 靖樹, 田中 恵太郎
  • Organizer: 第32回日本疫学会学術総会
• [Presentation] 遺伝的糖尿病リスクと死亡との関連:J-MICC Study (2022)
  • Author(s): 古川拓馬、西田裕一郎、原めぐみ、島ノ江千里 、岩坂知治、古賀佳代子、田中恵太郎
  • Organizer: 第33回日本疫学会学術総会
• [Presentation] 病型特異的な痛風関連遺伝子と適応進化の評価：臨床診断された痛風症例のゲノムワイド関連解析から (2021)
  • Author(s): 中山昌喜、中杤昌弘、河村優輔、山本健、中岡博史、清水聖子、小山晃英、栗木清典、大山博司、島ノ江千里、釜野桜子、前原一輝、桐原真奈、嶽崎俊郎、松尾恵太郎、鈴木貞夫、若井建志、岡田随象、四ノ宮成祥、松尾洋孝
  • Organizer: 第31回日本疫学会学術総会
• [Presentation] 日本人のストレス対処行動と腎機能との関連：J-MICC横断研究 (2021)
  • Author(s): 古賀 佳代子、原 めぐみ、島ノ江 千里、西田 裕一郎、古川 拓馬、岩坂知治、田中 恵太郎、 J-MICC Study Group
  • Organizer: 第31回日本疫学会学術総会
• [Presentation] うつ病バイオマーカーであるリン酸エタノールアミン(PEA)の酵素免疫測定法1 (2021)
  • Author(s): 斉田哲也、祖川倫太郎、野中竜稀、巴山 忠、冨田陵子、片岡裕登、門司 晃、溝口義人、島ノ江千里、進 正志
  • Organizer: 日本薬学会 第141年会
• [Presentation] ストレスマーカーとしての尿中コルチゾール/コルチゾン比の意義―スポット尿によるグルココルチコイド類測定の応用可能性― (2020)
  • Author(s): 島ノ江千里
  • Organizer: 第27回日本行動医学会学術総会
  • Invited
• [Presentation] 尿中cortisol/cortisone比と精神健康との関連：J-MICC study SAGA (2020)
  • Author(s): 島ノ江 千里、松本 明子、赤尾 千穂、原 めぐみ、西田 裕一郎、 南里 妃名子、堀田 美加子、山田 陽介、檜垣 靖樹、田中 恵太郎
  • Organizer: 第30回日本疫学会学術総会
• [Presentation] 慢性腎臓病と自覚ストレスとの関連：J-MICC横断研究 (2020)
  • Author(s): 古賀 佳代子、原 めぐみ、島ノ江 千里、西田 裕一郎、古川 拓馬、田中 恵太郎、 J-MICC Study Group
  • Organizer: 第30回日本疫学会学術総会
• [Presentation] メタボリックシンドロームと心理ストレスバイオマーカーとの関連 (2020)
  • Author(s): 島ノ江千里、松本明子、赤尾千穂、原めぐみ、西田裕一郎、堀田美加子、市場正良、田中恵太郎
  • Organizer: 第90回日本衛生学会学術総会
• [Presentation] 郵送法による10年後のコーホート追跡調査への回答と関連する要因:J‐MICC Study佐賀地区 (2019)
  • Author(s): 原めぐみ, 島ノ江千里, 西田裕一郎, 堀田美加子, 田中恵太郎
  • Organizer: 第29回日本疫学会学術総会
• [Presentation] 変異型ALDH2の新規表現型：飲酒誘導性メラニン沈着 (2019)
  • Author(s): 島ノ江千里、原俊哉 、赤尾千穂 、杠岳文、吉森 智香子、武藤 岳夫、遠藤光一、原めぐみ、市場正良、松本明子
  • Organizer: Aldh2ノックアウトマウス学会 第19回研究会
• [Presentation] 日本人のストレス対処行動に関するGWAS解析：JーMICC study (2019)
  • Author(s): 島ノ江 千里、八谷剛史、原 めぐみ、須藤洋一、西田 裕一郎、清水厚志、田中 恵太郎
  • Organizer: 第29回日本疫学会学術総会
• [Presentation] 日本人のストレス対処行動とFBXO45遺伝子との関連：J-MICC GWAS (2018)
  • Author(s): 島ノ江千里
  • Organizer: 第3回 ゲノムコホート研究における遺伝統計学
  • Invited
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