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Integrative analysis of genes associated with social behavior in Williams syndrome

Research Project

Project/Area Number 19K08251
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKyoto University

Principal Investigator

Kimura Ryo  京都大学, 医学研究科, 准教授 (20636641)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsウィリアムス症候群 / DNAメチル化 / ネットワーク解析
Outline of Research at the Start

本研究は、DNAメチル化変化を手がかりに、ウィリアムス症候群の社会行動異常に関わる遺伝子を見出すことを目的とする。ウィリアムス症候群は、7番染色体の片側にある複数の遺伝子の欠失により生じ、多彩な症状を呈することが知られている。しかし、その特徴的な症状である、過度な社交性に関わる遺伝子は不明である。本研究では、患者検体を使ってDNAメチル化変化を調べ、そのネットワーク解析から社会行動異常に関わる遺伝子を探索し、ゲノム編集技術を使って作成した変異ゼブラフィッシュを用いて社会性を評価する。本研究結果は、ウィリアムス症候群だけでなく、社会性の低下を来す自閉スペクトラム症の治療への応用が期待される。

Outline of Final Research Achievements

The purpose of this study was to find genes associated with social behavior in Williams syndrome (WS) based on DNA methylation changes. First, we obtained a significant number of blood samples from participants and performed comprehensive DNA methylation profiling. We then applied co-methylation network analysis to identified DNA methylation genes, and by combining this with clinical symptom evaluation, we were able to identify modules that were suggested to be associated with social behavior in WS. Interestingly, the hub gene which located in central to this network, were also significantly altered in the postmortem brains of WS patients. Thus, our study identified a group of genes that may be involved in social behavior in WS.

Academic Significance and Societal Importance of the Research Achievements

ウィリアムス症候群は、7番染色体の片側にある複数の遺伝子の欠失により生じ、高い社交性含む特徴的な症状から、近年非常に注目を集めている。しかし、これまでに欠失領域内の遺伝子研究や質問紙を用いた臨床研究が多く行われてきたが、行動異常など症状に関わる遺伝子については十分に解明されていなかった。本研究により、DNAメチル化異常がウィリアムス症候群の病態に関わっていることが明らかになった。これは、ウィリアムス症候群にみられる多彩な症状の原因を説明する重要な手がかりを与える知見であり、今後さらなる病態の飛躍的な解明につながることが期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (28 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (7 results) Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (5 results) (of which Int'l Joint Research: 2 results) Remarks (2 results)

  • [Int'l Joint Research] Maastricht University(オランダ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Harvard Medical School/University of California Los Angeles(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Gottingen(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Maastricht University(オランダ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Gottingen(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Harvard Medical School/University of California Los Angeles(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Seville(スペイン)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Comparison of the Social Responsiveness Scale-2 among Individuals with Autism Spectrum Disorder and Williams Syndrome in Japan2022

    • Author(s)
      Hirai Masahiro、Asada Kosuke、Kato Takeo、Ikeda Takahiro、Hakuno Yoko、Ikeda Ayaka、Matsushima Kanae、Awaya Tomonari、Okazaki Shin、Kato Toshihiro、Funabiki Yasuko、Murai Toshiya、Heike Toshio、Hagiwara Masatoshi、Yamagata Takanori、Tomiwa Kiyotaka、Kimura Ryo
    • Journal Title

      Journal of Autism and Developmental Disorders

      Volume: - Issue: 8 Pages: 3176-3184

    • DOI

      10.1007/s10803-022-05740-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cross-disorder analysis of genetic and regulatory copy number variations in bipolar disorder, schizophrenia, and autism spectrum disorder2022

    • Author(s)
      Kushima Itaru、Nakatochi Masahiro、Aleksic Branko、Okada Takashi、(中略)、Ozaki Norio
    • Journal Title

      Biological Psychiatry

      Volume: - Issue: 5 Pages: 362-374

    • DOI

      10.1016/j.biopsych.2022.04.003

    • 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] 高い社交性を呈する希少疾患、ウィリアムズ症候群2022

    • Author(s)
      木村亮
    • Journal Title

      難病と在宅ケア

      Volume: 28 Pages: 45-48

    • Related Report
      2022 Annual Research Report
  • [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] エピゲノム制御異常と精神神経疾患2021

    • Author(s)
      木村亮, 萩原正敏
    • Journal Title

      CSJカレントレビュー

      Volume: 39 Pages: 99-105

    • Related Report
      2021 Research-status Report
  • [Journal Article] Integrated DNA methylation analysis reveals a potential role for ANKRD30B in Williams syndrome2020

    • Author(s)
      Ryo Kimura, Roy Lardenoije, Kiyotaka Tomiwa, Yasuko Funabiki, Masatoshi Nakata, Shiho Suzuki, Tomonari Awaya, Takeo Kato, Shin Okazaki, Toshiya Murai, Toshio Heike, Bart P F Rutten, Masatoshi Hagiwara
    • Journal Title

      Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

      Volume: 45 Issue: 10 Pages: 1627-1636

    • DOI

      10.1038/s41386-020-0675-2

    • NAID

      120006840165

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Different effects of methylphenidate and atomoxetine on the behavior and brain transcriptome of zebrafish2020

    • Author(s)
      Shiho Suzuki, Ryo Kimura, Shingo Maegawa, Masatoshi Nakata, Masatoshi Hagiwara
    • Journal Title

      Molecular brain

      Volume: 13 Issue: 1 Pages: 70-70

    • DOI

      10.1186/s13041-020-00614-4

    • NAID

      120006843530

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder2020

    • Author(s)
      Kato Hidekazu、Kushima Itaru、Mori Daisuke、Yoshimi Akira、Aleksic Branko、Nawa Yoshihiro、Toyama Miho、Furuta Sho、Yu Yanjie、Ishizuka Kanako、Kimura Hiroki、Arioka Yuko、Tsujimura Keita、Morikawa Mako、Okada Takashi、Inada Toshiya、Nakatochi Masahiro、Shinjo Keiko、Kondo Yutaka、Kaibuchi Kozo、Egawa Jun et al
    • Journal Title

      Translational Psychiatry

      Volume: 10 Issue: 1 Pages: 421-421

    • DOI

      10.1038/s41398-020-01107-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulation of the oxytocin receptor gene in Williams syndrome2020

    • Author(s)
      Kimura Ryo、Tomiwa Kiyotaka、Inoue Ryo、Suzuki Shiho、Nakata Masatoshi、Awaya Tomonari、Kato Takeo、Okazaki Shin、Heike Toshio、Hagiwara Masatoshi
    • Journal Title

      Psychoneuroendocrinology

      Volume: 115 Pages: 104631-104631

    • DOI

      10.1016/j.psyneuen.2020.104631

    • NAID

      120006813279

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An epigenetic biomarker for adult high-functioning autism spectrum disorder2019

    • Author(s)
      Kimura Ryo、Nakata Masatoshi、Funabiki Yasuko、Suzuki Shiho、Awaya Tomonari、Murai Toshiya、Hagiwara Masatoshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 13662-13662

    • DOI

      10.1038/s41598-019-50250-9

    • NAID

      120006726165

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA profiling in adults with high-functioning autism spectrum disorder2019

    • Author(s)
      Nakata Masatoshi、Kimura Ryo、Funabiki Yasuko、Awaya Tomonari、Murai Toshiya、Hagiwara Masatoshi
    • Journal Title

      Molecular Brain

      Volume: 12 Issue: 1 Pages: 82-82

    • DOI

      10.1186/s13041-019-0508-6

    • NAID

      120006764460

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robust Candidates for Language Development and Evolution Are Significantly Dysregulated in the Blood of People With Williams Syndrome2019

    • Author(s)
      Benitez-Burraco Antonio、Kimura Ryo
    • Journal Title

      Frontiers in Neuroscience

      Volume: 13 Pages: 258-258

    • DOI

      10.3389/fnins.2019.00258

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 知っておきたい稀な精神症候・症候群―症例から学ぶ―14.ウィリアムズ症候群2019

    • Author(s)
      木村亮
    • Journal Title

      精神科治療学

      Volume: 34 Pages: 47-49

    • Related Report
      2019 Research-status Report
  • [Presentation] シンポジウム 自閉症スペクトラム症の新規病態と治療的展開 遺伝子発現に着目した自閉スペクトラム症の病態研究と治療の可能性2021

    • Author(s)
      木村亮
    • 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大会
    • Related Report
      2021 Research-status Report
  • [Presentation] シンポジウム 超社会性を呈する希少疾患に着目した社会性認知研究の現状と展望 超社会性を呈する希少疾患ウィリアムズ症候群とは2021

    • Author(s)
      木村亮
    • Organizer
      第117回 日本精神神経学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ゼブラフィッシュを活用した神経発達症研究の現状と課題2021

    • Author(s)
      木村亮, 鈴木志穂, 西村泰生, 前川真吾, 萩原正敏
    • Organizer
      第7回 ゼブラフィッシュ・メダカ創薬研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] Integrative DNA methylation and gene expression analysis of Williams syndrome2019

    • Author(s)
      Ryo Kimura, Roy Lardenoije, Kiyotaka Tomiwa, Yasuko Funabiki, Masatoshi Nakata, Shiho Suzuki, Tomonari Awaya, Takeo Kato, Toshiya Murai, Toshio Heike, Bart Rutten, Masatoshi Hagiwara
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Integrated Epigenetic Analysis of Williams Syndrome2019

    • Author(s)
      Ryo Kimura, Roy Lardenoije, Kiyotaka Tomiwa, Yasuko Funabiki, Masatoshi Nakata, Shiho Suzuki, Tomonari Awaya, Takeo Kato, Shin Okazaki, Toshiya Murai, Toshio Heike, Bart Rutten, Masatoshi Hagiwara
    • Organizer
      World Congress on Psychiatric Genetics 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] エピゲノム異常がウィリアムズ症候群に関わることを発見 -多彩な症状の原因を説明する手がかりに-

    • URL

      https://www.kyoto-u.ac.jp/ja/research-news/2020-04-24

    • Related Report
      2020 Research-status Report
  • [Remarks] 2種類のADHD治療薬が対照的な作用を持つことを発見 -ゼブラフィッシュで行動や脳での働きを探る-

    • URL

      https://www.kyoto-u.ac.jp/ja/research-news/2020-05-18-0

    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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