Search for schizophrenia risk gene based on whole-exome sequencing of parent-affected offspring trios, and gene expression analysis of postmortem brains

• Project/Area Number: 16K10185
• 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: Watanabe Yuichiro 新潟大学, 医歯学系, 准教授 (90401744)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 統合失調症

Outline of Final Research Achievements

Aim: Rare variations are suggested to play a role in the genetic etiology of schizophrenia, and to further investigate their role, we performed a three-stage study. Methods: First, we performed whole-exome sequencing (WES) of two parent-affected offspring trios. Second, we sequenced the FBXO18 coding region in 96 patients. Third, we tested rare non-synonymous FBXO18 variations for association with schizophrenia in 1,376 patients and 1,496 controls. Results: A rare frameshift variation (L116fsX) in the FBXO18 gene was recurrently identified by WES in both trios. Sequencing FBXO18 coding regions, we detected three rare non-synonymous variations (V15L, L116fsX and V1006I). However, these rare FBXO18 variations were not significantly associated with and schizophrenia in the case-control study. Conclusion: Our present study does not provide evidence for the contribution of rare non-synonymous FBXO18 variations to the genetic etiology of schizophrenia in the Japanese population.

Academic Significance and Societal Importance of the Research Achievements

本研究では統合失調症のリスク遺伝子を同定するには至らなかった。その主な理由として、サンプル数が十分でないことがあげられる。今後は自施設でのサンプル収集をさらに進めるとともに、多施設共同研究を拡大し、日本人は遺伝的な均質性が高いという利点をいかした優れた研究デザインを組むことで、統合失調症の発症に大きな効果をもつリスク遺伝子を確定できるものと予想される。

Research Products

• [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
• [Presentation] Rare FBXO18 variations and risk of schizophrenia (2018)
  • Author(s): Watanabe Y, Hoya S, Hishimoto A, Nunokawa A, Inoue E, Igeta H, Otsuka I, Shibuya M, Sora I, Someya T
  • Organizer: WFSBP Asia Pacific Regional Congress of Biological Psychiatry
  • Int'l Joint Research
• [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: 第39回日本生物学的精神医学会・第47回日本精神神経薬理学会合同年会