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Study of biomarker for youth suicide risk through genome and epigenome-wide data

Research Project

Project/Area Number 21K15712
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionKobe University

Principal Investigator

Otsuka Ikuo  神戸大学, 医学部附属病院, 助教 (40722880)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords若年自殺 / ゲノム / エピゲノム / バイオマーカー / リスクマーカー / メチル化年齢 / テロメア
Outline of Research at the Start

申請者らが網羅的ゲノム・エピゲノム解析により見出した、30歳代以下の自殺者における①末梢血テロメア異常短縮、②末梢血DNAメチル化年齢の異常老齢化、③自殺リスクに強く関連するGTF2IRD1遺伝子多型の存在、という予備的知見について、日本人若年自殺者及び、強い自殺念慮を有する若年者、さらには米国コロンビア大との連携による白人若年自殺行動者の追加試料を用いて多角的に追試し、臨床現場で真に有用な若年自殺リスクのバイオマーカーとなりうるかを検討する。

Outline of Final Research Achievements

Suicides (especially among young people) are increasing both in Japan and around the world. In this study, regarding youth suicide risk for which biomarkers and biological mechanisms have not yet been clarified, the novel preliminary findings "aberrant telomere shortening, abnormal acceleration of epigenetic age, and GTF2iRD1 SNP association in young suicides" that the applicant already identified were successfully replicated in an independent young suicide cohort. In addition, the applicant identified an aberrant increase in natural killer cells in juvenile suicides, and genetically mapped the correlation between suicidal behavior and other psychiatric traits classified into non-fatal suicide attempt and suicide death.

Academic Significance and Societal Importance of the Research Achievements

本研究の実施で、より強固なエビデンスが得られた「若年自殺リスクにおけるテロメア異常短縮・エピゲノム年齢異常老齢化・NK細胞異常増加」といったエピゲノムデータ由来の知見は、ケア介入によって可逆的な性質を有するものであり、また既に世界的に市販・流通しているアレイで容易に取得できる。本内容を引き続き大規模かつ経時的なデータで追試していくことで、「若年者の自殺リスクによる生物学的変化は、介入によって回復させることできる」というポジティブな科学的根拠に基づいて、新たなリスクマーカーパッケージやケアコンテンツ開発・創薬をスムーズに目指すことができる可能性がある。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (26 results)

All 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (20 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 18 results,  Open Access: 12 results) Presentation (2 results) (of which Invited: 1 results) Book (2 results)

  • [Int'l Joint Research] Columbia University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Columbia University(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Epigenetic clock analysis reveals increased plasma cystatin C levels based on DNA methylation in major depressive disorder.2023

    • Author(s)
      Tanifuji T, Okazaki S, Otsuka I, Mouri K, Horai T, Shindo R, Shirai T, Hishimoto A.
    • Journal Title

      Psychiatry Research

      Volume: Epub ahead of print Pages: 115103-115103

    • DOI

      10.1016/j.psychres.2023.115103

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ribosomal DNA gene copies are increased in blood and brain of Japanese schizophrenia patients2023

    • Author(s)
      Li Sen、Otsuka Ikuo、Tanifuji Takaki、Okazaki Satoshi、Horai Tadasu、Takahashi Motonori、Kondo Takeshi、Ueno Yasuhiro、Hishimoto Akitoyo
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 1 Pages: e0280694-e0280694

    • DOI

      10.1371/journal.pone.0280694

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans2023

    • Author(s)
      Kimbrel Nathan A.、Hishimoto Akitoyo、Okazaki Satoshi、Otsuka Ikuo、et al.
    • Journal Title

      JAMA Psychiatry

      Volume: 80 Issue: 2 Pages: 135-135

    • DOI

      10.1001/jamapsychiatry.2022.3896

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epigenetic clock analysis in methamphetamine dependence2022

    • Author(s)
      Takemura Yukihiro、Tanifuji Takaki、Okazaki Satoshi、Shinko Yutaka、Otsuka Ikuo、Horai Tadasu、Shirai Toshiyuki、Aso Katsuro、Yamamoto Noriya、Hishimoto Akitoyo
    • Journal Title

      Psychiatry Research

      Volume: 317 Pages: 114901-114901

    • DOI

      10.1016/j.psychres.2022.114901

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preventive effects of preoperative ramelteon on postoperative delirium in Asian elderly population: A randomized, double-blind, placebo-controlled trial, and a systematic review and meta-analysis2022

    • Author(s)
      Tanifuji Takaki、Otsuka Ikuo、Okazaki Satoshi、Horai Tadasu、So Ryuhei、Shiroiwa Kyoichi、Mouri Kentaro、Tanaka Motofumi、Ohmoto Nobuko、Sora Ichiro、Hirai Midori、Fukumoto Takumi、Ku Yonson、Hishimoto Akitoyo
    • Journal Title

      Asian Journal of Psychiatry

      Volume: 78 Pages: 103282-103282

    • DOI

      10.1016/j.ajp.2022.103282

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful electroconvulsive therapy for 22q11.2 deletion syndrome with Schizophrenia and Parkinson's disease2022

    • Author(s)
      Tanifuji Takaki、Otsuka Ikuo、Kimura Atsushi、Horai Tadasu、Okazaki Satoshi、Satake Wataru、Hishimoto Akitoyo
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 76 Issue: 11 Pages: 603-604

    • DOI

      10.1111/pcn.13467

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improving polygenic prediction in ancestrally diverse populations2022

    • Author(s)
      Ruan Yunfeng、Lin Yen-Feng、Feng Yen-Chen Anne、Chen Chia-Yen、Lam Max、Guo Zhenglin、Ahn Yong Min、Akiyama Kazufumi、Arai Makoto、Baek Ji Hyun、Chen Wei J.、Chung Young-Chul、Feng Gang、Fujii Kumiko、et al. 50名、Stanley Global Asia Initiatives
    • Journal Title

      Nature Genetics

      Volume: 54 Issue: 5 Pages: 573-580

    • DOI

      10.1038/s41588-022-01054-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epigenetic aging in Williams syndrome2022

    • Author(s)
      Okazaki Satoshi、Kimura Ryo、Otsuka Ikuo、Tomiwa Kiyotaka、Funabiki Yasuko、Hagiwara Masatoshi、Murai Toshiya、Hishimoto Akitoyo
    • Journal Title

      Journal of Child Psychology and Psychiatry

      Volume: 63 Issue: 12 Pages: 1553-1562

    • DOI

      10.1111/jcpp.13613

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polymorphisms in the hypoxia inducible factor binding site of the macrophage migration inhibitory factor gene promoter in schizophrenia2022

    • Author(s)
      Okazaki Satoshi、Boku Shuken、Watanabe Yuichiro、Otsuka Ikuo、Horai Tadasu、Morikawa Ryo、Kimura Atsushi、Shimmyo Naofumi、Tanifuji Takaki、Someya Toshiyuki、Hishimoto Akitoyo
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 3 Pages: e0265738-e0265738

    • DOI

      10.1371/journal.pone.0265738

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel missense SETD1A variants in Japanese patients with schizophrenia: Resequencing and association analysis2022

    • Author(s)
      Morikawa Ryo、Watanabe Yuichiro、Igeta Hirofumi、Arta Reza K.、Ikeda Masashi、Okazaki Satoshi、Hoya Satoshi、Saito Takeo、Otsuka Ikuo、Egawa Jun、Tanifuji Takaki、Iwata Nakao、Someya Toshiyuki
    • Journal Title

      Psychiatry Research

      Volume: 310 Pages: 114481-114481

    • DOI

      10.1016/j.psychres.2022.114481

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic clock analysis and increased plasminogen activator inhibitor-1 in high-functioning autism spectrum disorder2022

    • Author(s)
      Okazaki Satoshi、Kimura Ryo、Otsuka Ikuo、Funabiki Yasuko、Murai Toshiya、Hishimoto Akitoyo
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 2 Pages: e0263478-e0263478

    • DOI

      10.1371/journal.pone.0263478

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accelerated epigenetic age and shortened telomere length based on DNA methylation in Nicolaides?Baraitser syndrome2022

    • Author(s)
      Shinko Yutaka、Okazaki Satoshi、Otsuka Ikuo、Horai Tadasu、Kim Saehyeon、Tanifuji Takaki、Hishimoto Akitoyo
    • Journal Title

      Molecular Genetics & Genomic Medicine

      Volume: 10 Issue: 3

    • DOI

      10.1002/mgg3.1876

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors2022

    • Author(s)
      Mullins N, Ikuo Otsuka, Akitoyo Hishimoto et al.
    • Journal Title

      Biological Psychiatry

      Volume: 91 Issue: 3 Pages: 313-327

    • DOI

      10.1016/j.biopsych.2021.05.029

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits2021

    • Author(s)
      Otsuka Ikuo、Galfalvy Hanga、Guo Jia、Akiyama Masato、Rujescu Dan、Turecki Gustavo、Hishimoto Akitoyo、Mann J. John
    • Journal Title

      Psychological Medicine

      Volume: Epub Issue: 6 Pages: 1-9

    • DOI

      10.1017/s0033291721004700

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Searching for biomarkers in schizophrenia and psychosis: Case‐control study using capillary electrophoresis and liquid chromatography time‐of‐flight mass spectrometry and systematic review for biofluid metabolites2021

    • Author(s)
      Kim Saehyeon、Okazaki Satoshi、Otsuka Ikuo、Shinko Yutaka、Horai Tadasu、Shimmyo Naofumi、Hirata Takashi、Yamaki Naruhisa、Tanifuji Takaki、Boku Shuken、Sora Ichiro、Hishimoto Akitoyo
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 42 Issue: 1 Pages: 42-51

    • DOI

      10.1002/npr2.12223

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A preliminary genetic association study of GAD1 and GABAB receptor genes in patients with treatment-resistant schizophrenia2021

    • Author(s)
      Miyazawa Atsuhiro、Kanahara Nobuhisa、Kogure Masanobu、Otsuka Ikuo、Okazaki Satoshi、Watanabe Yoshinori、Yamasaki Fumiaki、Nakata Yusuke、Oda Yasunori、Hishimoto Akitoyo、Iyo Masaomi
    • Journal Title

      Molecular Biology Reports

      Volume: 49 Issue: 3 Pages: 2015-2024

    • DOI

      10.1007/s11033-021-07019-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of Two Variable Number of Tandem Repeats in the Monoamine Oxidase A Gene Promoter with Schizophrenia2021

    • Author(s)
      Tanifuji Takaki、Okazaki Satoshi、Otsuka Ikuo、Horai Tadasu、Shinko Yutaka、Kim Saehyeon、Sora Ichiro、Hishimoto Akitoyo
    • Journal Title

      Neuropsychiatric Disease and Treatment

      Volume: Volume 17 Pages: 3315-3323

    • DOI

      10.2147/ndt.s338854

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum levels of glial cell line-derived neurotrophic factor as a biomarker for mood disorders and lithium response2021

    • Author(s)
      Keita Idemoto, Tamaki Ishima, Tomihisa Niitsu, Tatsuki Hata, Sumiko Yoshida, Kotaro Hattori, Tadasu Horai, Ikuo Otsuka, Hidenaga Yamamori, Shigenobu Toda etc
    • Journal Title

      Psychiatric Res

      Volume: 301 Pages: 113967-113967

    • DOI

      10.1016/j.psychres.2021.113967

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 臨床での活用が期待される自殺の生物学的知見2021

    • Author(s)
      大塚郁夫, 菱本明豊.
    • Journal Title

      医学のあゆみ

      Volume: 279(1) Pages: 29-34

    • Related Report
      2021 Research-status Report
  • [Journal Article] 自殺の神経生物学的異常2021

    • Author(s)
      大塚郁夫, 菱本明豊.
    • Journal Title

      臨床精神医学

      Volume: 50(6) Pages: 577-583

    • Related Report
      2021 Research-status Report
  • [Presentation] ゲノム/エピゲノム解析からみた自殺と細胞老化2022

    • Author(s)
      大塚郁夫
    • Organizer
      BPCNPNPPP4学会合同年会(東京)
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 日本人自殺者のゲノムワイド関連解析2021

    • Author(s)
      大塚郁夫
    • Organizer
      第43回日本生物学的精神医学会・第51回日本神経精神薬理学会合同年会
    • Related Report
      2021 Research-status Report
  • [Book] 臨床での活用が期待される自殺の生物学的知見(別冊・医学のあゆみ)2022

    • Author(s)
      大塚郁夫、菱本明豊
    • Total Pages
      101
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2022 Annual Research Report
  • [Book] 不安と自殺・自傷 ー特に遺伝学的知見の観点からー(臨床精神医学)2022

    • Author(s)
      大塚郁夫、谷藤貴紀
    • Total Pages
      1088
    • Publisher
      アークメディア
    • Related Report
      2022 Annual Research Report

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Published: 2021-04-28   Modified: 2024-01-30  

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