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2021 Fiscal Year Annual Research Report

ポリジェニックリスクスコアを用いた自殺リスクの予測と遺伝学的解明

Research Project

Project/Area Number 21H02852
Research InstitutionYokohama City University

Principal Investigator

菱本 明豊  横浜市立大学, 医学研究科, 教授 (50529526)

Co-Investigator(Kenkyū-buntansha) 秋山 雅人  九州大学, 医学研究院, 講師 (10757686)
曳野 圭子  国立研究開発法人理化学研究所, 生命医科学研究センター, 特別研究員 (10789580)
大塚 郁夫  神戸大学, 医学部附属病院, 助教 (40722880)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywords自殺 / ポリジェニックリスクスコア / ゲノムワイド関連解析
Outline of Annual Research Achievements

自殺についての遺伝学的知見の獲得は、自殺者試料の収集が困難なため世界的に大幅に遅れている。申請者らは国内唯一・世界最大規模の自殺者DNA試料とゲノムワイド関連解析(genome-wide association study; GWAS)データを有し、GWASデータから算出できる個人ごとの自殺ポリジェニックリスクスコア(polygenic risk score; PRS)が、個人の自殺リスクを予測できる可能性を見出した。本研究では、自殺者/自殺未遂者試料の追加GWASを実施し計1,800例の日本人自殺者/自殺未遂者(及び20,000例の非自殺者)のGWASデータを用いることで、①日本人集団において自殺PRSがどの程度の確度で自殺リスクを予測できるか、②アジア人種において各精神疾患や喫煙・飲酒・身長・体重などの様々なヒト表現型がどの程度自殺と遺伝的リスクを共有しているか、の2点を精細に検討する。R3年度末までに約400例の自殺関連試料の追加収集・大部分のGWASデータ取得を実施し、次年度以降の解析に向けて順調に準備を進めることができた。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

予定していたサンプル数の自殺関連試料のGWASデータを取得できている。また理化学研究所との連携によるコントロールデータの確保・品質管理や、遺伝学的統計解析手法の洗練含め、次年度の解析に向けて順調に準備を進めることができている。

Strategy for Future Research Activity

本研究では、申請者らが自身でスケールアップする自殺者/自殺未遂者GWASのデータを用いることで、日本人集団において自殺PRSがどの程度の確度で自殺リスクを予測できるかを検討することを主目的としているが、申請者らは現在「精神疾患患者における自殺PRSの自殺リスク予測精度」の解析も併行して行っており、本研究の成果との統合・比較を通して、「精神科臨床現場における自殺リスクを把握しての自殺予防臨床」への貢献も目指している。

  • Research Products

    (27 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (25 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 23 results,  Open Access: 16 results) Presentation (1 results)

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

    • Country Name
      U.S.A.
    • Counterpart Institution
      Columbia University
  • [Journal Article] Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits2023

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

      Psychological Medicine

      Volume: 53 Pages: 2689~2697

    • DOI

      10.1017/S0033291721004700

    • Peer Reviewed
  • [Journal Article] Problematic Internet use and daily difficulties among adolescents with school refusal behaviors2022

    • Author(s)
      Fujita Junichi、Aoyama Kumi、Saigusa Yusuke、Miyazaki Hidehito、Aoki Yoshiko、Asanuma Kazuya、Takahashi Yuichi、Hishimoto Akitoyo
    • Journal Title

      Medicine

      Volume: 101 Pages: e28916~e28916

    • DOI

      10.1097/MD.0000000000028916

    • Peer Reviewed / Open Access
  • [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 Pages: e0265738

    • DOI

      10.1371/journal.pone.0265738

    • Peer Reviewed / Open Access
  • [Journal Article] Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry2022

    • Author(s)
      Ogasawara Kazuyoshi, Ikuo Otsuka, Akitoyo Hishimoto et al.
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: Epub Pages: Epub

    • DOI

      10.1002/npr2.12245

    • Peer Reviewed / Open Access
  • [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 Pages: e0263478

    • DOI

      10.1371/journal.pone.0263478

    • 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 Pages: e1876

    • DOI

      10.1002/mgg3.1876

    • Peer Reviewed / Open Access
  • [Journal Article] The characteristics of patients receiving psychotropic pro re nata medication at discharge for the treatment of schizophrenia and major depressive disorder: A nationwide survey from the EGUIDE project2022

    • Author(s)
      Ichihashi Kayo, Ikuo Otsuka, Akitoyo Hishimoto et al.
    • Journal Title

      Asian Journal of Psychiatry

      Volume: 69 Pages: 103007~103007

    • DOI

      10.1016/j.ajp.2022.103007

    • Peer Reviewed
  • [Journal Article] Structural brain abnormalities in adolescent patients with anorexia nervosa at both the acute and weight-recovered phase2022

    • Author(s)
      Asami Takeshi、Takaishi Masao、Nakamura Ryota、Yoshimi Asuka、Konishi Jun、Aoyama Kumi、Fujita Junichi、Miyazaki Hidehito、Aoki Yoshiko、Asanuma Kazuya、Hattori Saki、Suda Akira、Whitford Thomas J.、Hirayasu Yoshio、Hishimoto Akitoyo
    • Journal Title

      Brain Imaging and Behavior

      Volume: Epub Pages: Epub

    • DOI

      10.1007/s11682-021-00622-5

    • Peer Reviewed
  • [Journal Article] Hypnotic medication use among inpatients with schizophrenia and major depressive disorder: results of a nationwide study2022

    • Author(s)
      Furihata Ryuji, Akitoyo Hishimoto et al.
    • Journal Title

      Sleep Medicine

      Volume: 89 Pages: 23~30

    • DOI

      10.1016/j.sleep.2021.11.005

    • Peer Reviewed
  • [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 Pages: 313~327

    • DOI

      10.1016/j.biopsych.2021.05.029

    • Peer Reviewed / Open Access / 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 Pages: 42~51

    • DOI

      10.1002/npr2.12223

    • Peer Reviewed / Open Access
  • [Journal Article] Association between the examination rate of treatment‐resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study2021

    • Author(s)
      Yasui‐Furukori Norio, Akitoyo Hishimoto et al.
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 42 Pages: 3~9

    • DOI

      10.1002/npr2.12218

    • 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 Pages: 2015~2024

    • DOI

      10.1007/s11033-021-07019-z

    • 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

    • Peer Reviewed / Open Access
  • [Journal Article] Japanese Project for Telepsychiatry Evaluation during COVID-19: Treatment Comparison Trial (J-PROTECT): Rationale, design, and methodology2021

    • Author(s)
      Kishimoto Taishiro, Akitoyo Hishimoto et al.
    • Journal Title

      Contemporary Clinical Trials

      Volume: 111 Pages: 106596

    • DOI

      10.1016/j.cct.2021.106596

    • Peer Reviewed / Open Access
  • [Journal Article] First case of Myhre syndrome with schizophrenia2021

    • Author(s)
      Inoue Keisuke、Eiro Tsuyoshi、Semoto Misato、Roppongi Tomohide、Nomoto Munetaka、Takahashi Yuichi、Hishimoto Akitoyo
    • Journal Title

      Clinical Dysmorphology

      Volume: 30 Pages: 207~208

    • DOI

      10.1097/MCD.0000000000000386

    • Peer Reviewed / Open Access
  • [Journal Article] Association between suicidal behaviors and auditory and visual hallucinations in Japanese adolescent psychiatric outpatients at first visit: a cross‐sectional study2021

    • Author(s)
      Toyohara Nao、Fujita Junichi、Okumura Yasuyuki、Suda Akira、Hattori Saki、Saigusa Yusuke、Aoyama Kumi、Asanuma Kazuya、Takahashi Yuichi、Arai Takashi、Hishimoto Akitoyo
    • Journal Title

      Child and Adolescent Mental Health

      Volume: Epub Pages: Epub

    • DOI

      10.1111/camh.12504

    • Peer Reviewed
  • [Journal Article] A Severe Dementia Case in End of Life Care with Psychiatric Symptoms Treated by Perampanel2021

    • Author(s)
      Kumamoto Asaki、Chiba Yuhei、Suda Akira、Hishimoto Akitoyo、Kase Akihiko
    • Journal Title

      Journal of Epilepsy Research

      Volume: 11 Pages: 93~95

    • DOI

      10.14581/jer.21012

    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics of discharge prescriptions for patients with schizophrenia or major depressive disorder: Real-world evidence from the Effectiveness of Guidelines for Dissemination and Education (EGUIDE) psychiatric treatment project2021

    • Author(s)
      Hashimoto Naoki, Hishimoto Akitoyo, et al.
    • Journal Title

      Asian Journal of Psychiatry

      Volume: 63 Pages: 102744~102744

    • DOI

      10.1016/j.ajp.2021.102744

    • Peer Reviewed / Open Access
  • [Journal Article] Three-Dimensional Convolutional Autoencoder Extracts Features of Structural Brain Images With a “Diagnostic Label-Free” Approach: Application to Schizophrenia Datasets2021

    • Author(s)
      Yamaguchi Hiroyuki、Hashimoto Yuki、Sugihara Genichi、Miyata Jun、Murai Toshiya、Takahashi Hidehiko、Honda Manabu、Hishimoto Akitoyo、Yamashita Yuichi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 652987

    • DOI

      10.3389/fnins.2021.652987

    • Peer Reviewed / Open Access
  • [Journal Article] Psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 pandemic2021

    • Author(s)
      Obata Soichiro、Miyagi Etsuko、Haruyama Yasuo、Umazume Takeshi、Kobashi Gen、Yoshimi Asuka、Hishimoto Akitoyo、Kurasawa Kentaro、Suzuki Yukio、Ikeda Tomoaki、Kimura Tadashi、Yamada Hideto
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 47 Pages: 2990~3000

    • DOI

      10.1111/jog.14877

    • 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)
      Idemoto Keita, Ikuo Otsuka, Akitoyo Hishimoto et al.
    • Journal Title

      Psychiatry Research

      Volume: 301 Pages: 113967~113967

    • DOI

      10.1016/j.psychres.2021.113967

    • Peer Reviewed
  • [Journal Article] Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study2021

    • Author(s)
      Numata Shusuke, Hishimoto Akitoyo, et al.
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 41 Pages: 199~206

    • DOI

      10.1002/npr2.12173

    • Peer Reviewed / Open Access
  • [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

  • [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

  • [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, 菱本明豊.
    • 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

URL: 

Published: 2022-12-28  

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