Genome-wide methylation and association analysis of depression

• Project/Area Number: 25461723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Teikyo Heisei University (2015-2016); The University of Tokyo (2013-2014)
• Principal Investigator: OTOWA Takeshi 帝京平成大学, 臨床心理学研究科, 教授 (70456119)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝子 / 全ゲノム関連解析 / うつ状態 / メチル化 / 環境 / ストレス / パイロシークエンス / SNP / 候補遺伝子 / セロトニントランスポーター / うつ病 / 一塩基多型 / 環境ストレス

Outline of Final Research Achievements

The aim of the present study is to identify genes that influence the association of stressful events with depression. Therefore, we performed a genome-wide G × E interaction analysis in the Japanese population living in the Kanto area (n=800) and found a nominally significant association. We also performed an epigenome-wide association study of depression using DNA methylation arrays and found several candidate regions.

Research Products

• [Journal Article] The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population. (2016)
  • Author(s): Otowa T, Kawamura Y, Tsutsumi A, Kawakami N, Kan C, Shimada T, Umekage T,Kasai K, Tokunaga K, Sasaki T.
  • Journal Title: PLoS One Volume: 11 Issue: 8 Pages: 1-14
  • DOI: 10.1371/journal.pone.0160823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations. (2016)
  • Author(s): 2. Liu X, Shimada T, Otowa T, Wu YY, Kawamura Y, Tochigi M, Iwata Y, Umekage T, Toyota T, Maekawa M, Iwayama Y, Suzuki K, Kakiuchi C, Kuwabara H, Kano Y, Nishida H, Sugiyama T, Kato N, Chen CH, Mori N, Yamada K, Yoshikawa T, Kasai K, Tokunaga K, Sasaki T, Gau SS.
  • Journal Title: Autism Res. Volume: 9 Issue: 3 Pages: 340-9
  • DOI: 10.1002/aur.1536
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Meta-analysis of genome-wide association studies of anxiety disorders. (2016)
  • Author(s): Otowa T, Hek K, Lee M, Byrne EM, Mirza SS, Nivard MG, Bigdeli T, et al.
  • Journal Title: Mol Psychiatry Volume: in press Issue: 10 Pages: 1391-1399
  • DOI: 10.1038/mp.2015.197
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Polymorphisms in the TMEM132D region are associated with panic disorder in HLA-DRB1*13:02-negative individuals of a Japanese population. (2016)
  • Author(s): Shimada-Sugimoto M, Otowa T, Miyagawa T, Khor S-S, Omae Y, Toyo-oka L, Sugaya N, Kawamura Y, Umekage T, Miyashita A, Kuwano R, Kaiya H, Kasai K, Tanii H, Okazaki Y, Tokunaga K, Sasaki T
  • Journal Title: Human Genome Variation Volume: 3 Issue: 1 Pages: 16001-16001
  • DOI: 10.1038/hgv.2016.1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immune-related pathways including HLA-DRB1(*)13:02 are associated with panic disorder. (2015)
  • Author(s): Shimada-Sugimoto M ほか
  • Journal Title: Brain Behav Immun Volume: Epub Pages: 96-103
  • DOI: 10.1016/j.bbi.2015.01.002
  • Peer Reviewed
• [Journal Article] Anger tendency may be associated with duration of illness in panic disorder. (2015)
  • Author(s): Sugaya N, Yoshida E, Yasuda S, Tochigi M, Takei K, Otowa T, Umekage T, Konishi Y, Sakano Y, Nomura S, Okazaki Y, Kaiya H, Tanii H, Sasaki T,
  • Journal Title: BioPsychoSocial Medicine Volume: 9 Issue: 1 Pages: 1-6
  • DOI: 10.1186/s13030-015-0035-3
  • Peer Reviewed / Open Access
• [Journal Article] A polymorphism in CCR1/CCR3 is associated with narcolepsy. (2015)
  • Author(s): Toyoda H, Miyagawa T, Koike A, Kanbayashi T, Imanishi A, Sagawa Y, Kotorii N, Kotorii T, Hashizume Y, Ogi K, Hiejima H, Kamei Y, Hida A, Miyamoto M, Imai M, Fujimura Y, Tamura Y, Ikegami A, Wada Y, Moriya S, Furuya H, Takeuchi M, Kirino Y, Meguro A, Remmers EF, Kawamura Y, Otowa T, Miyashita A, et al.
  • Journal Title: Brain Behav Immun. Volume: 印刷中 Pages: 148-155
  • DOI: 10.1016/j.bbi.2015.05.003
  • Peer Reviewed
• [Journal Article] Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals. (2015)
  • Author(s): Liu X, Kawashima M, Miyagawa T, Otowa T, Latt KZ, Thiri M, Nishida H, Sugiyama T, Tsurusaki Y, Matsumoto N, Mabuchi A, Tokunaga K, Sasaki T.
  • Journal Title: Human Genome Variation Volume: 2 Issue: 1 Pages: 15024-15024
  • DOI: 10.1038/hgv.2015.24
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Candidate Genes in Panic Disorder: Meta-Analyses of 23 Common Variants in Major Anxiogenic Pathways. (2015)
  • Author(s): Howe AS, Buttenschon H, Bani-Fatemi A, Maron E, Otowa T, Erhardt A, Binder EB, Gregersen N, Domschke K, Reif A, Shlik J, Koks S, Kawamura Y, Miyashita A, Kuwano R, Tokunaga K, Tanii H, Sasaki T, Smoller JW, De Luca1 V
  • Journal Title: Molecular Psychiatry Volume: 20 Issue: 5 Pages: 1-15
  • DOI: 10.1038/mp.2015.138
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The impact of childhood parental loss on risk for mood, anxiety and substance use disorders in a population-based sample of male twins. (2014)
  • Author(s): Otowa T, York TP, Gardner CO, Kendler KS, Hettema JM
  • Journal Title: Psychiatry Research Volume: 220 Issue: 1-2 Pages: 404-409
  • DOI: 10.1016/j.psychres.2014.07.053
  • Peer Reviewed
• [Journal Article] Genome-wide and gene-based association studies of anxiety disorders in European and African American samples. (2014)
  • Author(s): Otowa T, Maher BS, Aggen SH, McClay JL, van den Oord EJ, Hettema JM
  • Journal Title: Plos One Volume: 9 Issue: 11 Pages: e112559-e112559
  • DOI: 10.1371/journal.pone.0112559
  • Peer Reviewed / Open Access
• [Journal Article] 不安障害の遺伝研究 (2014)
  • Author(s): 音羽健司
  • Journal Title: 不安障害研究 Volume: 5 Pages: 73-84
  • NAID: 130004568117
  • Peer Reviewed
• [Journal Article] 糖尿病とうつ病 (2014)
  • Author(s): 音羽健司
  • Journal Title: 精神科 Volume: ２４ Pages: 295-300
• [Journal Article] 生活習慣病としてのうつ病 (2013)
  • Author(s): 音羽健司
  • Journal Title: 精神科 Volume: ２２ Pages: 38-43
• [Presentation] Epigenome-wide association analysis of DNA methylation in panic disorder. (2016)
  • Author(s): Shimada-Sugimoto M, Otowa T, Miyagawa T, Sugaya N, Kawamura Y, Umekage T, Kaiya H, Kasai K, Tanii H, Okazaki Y, Tokunaga K, Sasaki T
  • Organizer: The 66th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Vancouver (Canada)
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Genome-wide Methylation Analysis of Depression in the Japanese Population. (2015)
  • Author(s): Takeshi Otowa, Mihoko Shimada-Sugimoto, Taku Miyagawa, Yoshiya Kawamura, Chihiro Kakiuchi, Tadashi Uekage, Kiyoto Kasai, Katsushi Tokunaga, Tsukasa Sasaki.
  • Organizer: The 23th World Congress of Psychiatric Genetics
  • Place of Presentation: トロント (カナダ）
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Presentation] パニック障害 GWAS データに基づくパスウェイ解析とHLA についての解析 (2014)
  • Author(s): 杉本美穂子、音羽健司、梅景正、宮川卓、柏瀬貢一、吉田栄治、小島裕人、笠井清登、貝谷久宣、岡崎 祐士、谷井 久志、徳永 勝士、佐々木司
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: タワーホール船橋，東京
  • Year and Date: 2014-11-21
• [Presentation] パニック障害に関連する遺伝要因の探索 -GWASデータに基づくパスウェイ解析 (2014)
  • Author(s): 杉本美穂子、音羽健司、梅景正、宮川卓、柏瀬貢一、吉田栄治、小島裕人、笠井清登、貝谷久宣、岡崎 祐士、谷井 久志、徳永 勝士、佐々木司
  • Organizer: 第23回 日本組織適合性学会大会
  • Place of Presentation: 長崎大学医学部キャンパス，長崎
  • Year and Date: 2014-09-14
• [Presentation] RGS10遺伝子はストレスライフイベントとの交互作用を通じてうつ状態のリスクに関与する (2014)
  • Author(s): 音羽健司
  • Organizer: 第6回日本不安障害学会学術大会
  • Place of Presentation: 東京大学
• [Presentation] Genome-wide gene-environment study identifies Regulator of G-protein signaling-10 as a susceptibility gene for depression via stressful life events. (2013)
  • Author(s): Otowa T
  • Organizer: The 20th annual World Congress of Psychiatric Genetics
  • Place of Presentation: Boston, USA
• [Presentation] 精神疾患の遺伝環境交互作用 (2013)
  • Author(s): 音羽健司
  • Organizer: 平成25年度文部科学省科学研究費新学術領域研究「現代社会の階層化の機構理解と格差の制御：社会科学と健康科学の融合」第4回定例研究交流会シンポジウム
  • Place of Presentation: 東京大学