Investigation of a risk gene for schizophrenia starting from whole-exome sequencing in a Japanese multiplex family and expression analysis in postmortem brain

• Project/Area Number: 15K09802
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Niigata University
• Principal Investigator: NUNOKAWA AYAKO 新潟大学, 医歯学総合研究科, 客員研究員 (90584607)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 統合失調症 / エクソーム解析

Outline of Final Research Achievements

Rare genomic variations inherited in multiplex schizophrenia families are suggested to play a role in the genetic etiology of the disease. To identify rare variations with large effects on the risk of developing schizophrenia, we performed whole-exome sequencing(WES) in a multiplex family. We also performed follow-up resequencing of a potential risk gene identified by WES in the multiplex family and affected offspring of trios. Subsequently, we undertook a case-control study to investigate association between a potential risk gene and schizophrenia. A rare missense variation in UNC13B was identified by WES in multiplex family. Resequencing UNC13B coding regions identified five rare missense variations. In the case-control study, there were no significant association between rare missense UNC13B variations and schizophrenia. The present study did not provide supportive evidence for the contribution of UNC13B to susceptibility to schizophrenia in the Japanese population.

Research Products

• [Journal Article] Rare PDCD11 variations are not associated with risk of schizophrenia in Japan (2017)
  • Author(s): Hoya Satoshi、Watanabe Yuichiro、Hishimoto Akitoyo、Nunokawa Ayako、Kaneko Naoshi、Muratake Tatsuyuki、Shinmyo Naofumi、Otsuka Ikuo、Okuda Shujiro、Inoue Emiko、Igeta Hirofumi、Shibuya Masako、Egawa Jun、Orime Naoki、Sora Ichiro、Someya Toshiyuki
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 71 Issue: 11 Pages: 780-788
  • DOI: 10.1111/pcn.12549
  • Peer Reviewed / Open Access
• [Journal Article] Rare FBOX18 variations and risk of schizophrenia: whole-exome sequencing in two parent-affected offspring trios followed by resequencing and case-control studies. (2017)
  • Author(s): Hoya S, Watabe Y, Hishimoto A, Nunokawa A, Inoue E, Igeta H, Otsuka I, Shibuya M, Egawa J, Sora I, Someya T
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 印刷中 Issue: 8 Pages: 562-568
  • DOI: 10.1111/pcn.12526
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High-resolution copy number variation analysis of schizophrenia in Japan. (2017)
  • Author(s): Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, Kimura H, Takasaki Y, Wang C, Xing J, Ishizuka K, Oya-Ito T, Nakamura Y, Arioka Y, Maeda T, Yamamoto M, Yoshida M, Noma H, Hamada S, Morikawa M, Uno Y, Okada T, Iidaka T, Iritani S, Yamamoto T,
  • Journal Title: Molecular Psychiatry Volume: 22 Issue: 3 Pages: 430-440
  • DOI: 10.1038/mp.2016.88
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rare UNC13B variations and risk of schizophrenia: Whole- exome sequencing in a multiplex family and follow-up resequencing and a case-control study. (2016)
  • Author(s): Egawa J, Hoya S, Watanabe Y, Nunokawa A, Shibuya M, Ikeda M, Inoue E, Okuda S, Kondo K, Saito T, Kaneko N, Muratake T, Igeta H, Iwata N, Someya T
  • Journal Title: American Journal of medical genetics Volume: 14 Issue: 6 Pages: 797-805
  • DOI: 10.1002/ajmg.b.32444
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rare truncating variations and risk of schizophrenia: Whole-exome sequencing in three families with affected siblings and a three-stage follow-up study in a Japanese population. (2016)
  • Author(s): Watanabe Y, Nunokawa A, Shibuya M, Ikeda M, Hishimoto A, Kondo K, Egawa J, Kaneko N, Muratake T, Saito T, Okazaki S, Shimasaki A, Igeta H, Inoue E, Hoya S, Sugai T, Sora I, Iwata N, Someya T
  • Journal Title: Psychiatry Research Volume: 235 Pages: 13-18
  • DOI: 10.1016/j.psychres.2015.12.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] FBXO18遺伝子の稀な変異と統合失調症のリスク (2017)
  • Author(s): 布川綾子，保谷智史，渡部雄一郎，井上絵美子，井桁裕文，澁谷雅子，江川純，染矢俊幸
  • Organizer: 日本生物学的精神医学会
• [Presentation] SETD1A遺伝子の稀な変異と統合失調症の発症リスク (2017)
  • Author(s): 渡部雄一郎，井桁裕文，保谷智史，布川綾子，井上絵美子，江川純，澁谷雅子，染矢俊幸
  • Organizer: 日本生物学的精神医学会
• [Presentation] PDCD11遺伝子の稀な変異と統合失調症の発症リスク：罹患同胞対家系の全エクソーム解析、ターゲットリシーケンス、および症例・対照研究 (2017)
  • Author(s): 保谷智史，渡部雄一郎，菱本明豊，布川綾子，金子尚史，村竹辰之，新名尚史，大塚郁夫，奥田修二郎，井上絵美子，井桁裕文，澁谷雅子，江川純，折目直樹，曽良一郎，染矢俊幸
  • Organizer: 日本生物学的精神医学会
• [Presentation] はとこ婚の両親を持つ統合失調症罹患同胞家系のエクソーム解析 (2017)
  • Author(s): 井桁裕文，渡部雄一郎，布川綾子，井上絵美子，保谷智史，澁谷雅子，江川純，染矢俊幸
  • Organizer: 日本生物学的精神医学会
• [Presentation] 統合失調症罹患同胞対・両親3家系のエクソーム解析および3段階関連解析 (2016)
  • Author(s): 布川綾子，渡部雄一郎，澁谷雅子，池田匡志，菱本明豊，近藤健治，江川純，金子尚史，村竹辰之，齋藤竹生，岡崎賢志，島崎愛夕，井桁裕文，井上絵美子，保谷智史，須貝拓朗，曽良一郎，岩田仲生，染矢俊幸
  • Organizer: 日本生物学的精神医学会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-09-08
• [Presentation] UNB13B遺伝子の稀な変異と統合失調症のリスク (2016)
  • Author(s): 渡部雄一郎，江川純，保谷智史，布川綾子，澁谷雅子，池田匡志，井上絵美子，奥田修二郎，近藤賢治，齋藤竹生，金子尚史，村竹辰之，井桁裕文，岩田仲生，染矢俊幸
  • Organizer: 日本生物学的精神医学会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-09-08
• [Presentation] PDCD11遺伝子の稀な変異と統合失調症の発症リスク：罹患同胞対・両親3家系の全エクソーム解析 (2016)
  • Author(s): 保谷智史，渡部雄一郎，布川綾子，金子尚史，村竹辰之，井上絵美子，澁谷雅子，井桁裕文，江川純，染矢俊幸
  • Organizer: 日本生物学的精神医学会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-09-08
• [Presentation] BDNF遺伝子のC270T多型と統合失調症との関連：最新のメタ解析 (2015)
  • Author(s): 布川綾子， 渡部雄一郎， 染矢俊幸
  • Organizer: 第37回日本生物学的精神医学会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-09-24