Genome-Wide Association Studies of comprehensive cognitive function in Schizophrenia

• Project/Area Number: 15K19726
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: KUDO NORIKO 大阪大学, 連合小児発達学研究科, 特任研究員 (30751151)
• Research Collaborator: HASHIMOTO Ryota 大阪大学, 大学院連合小児発達学研究科・医学系研究科, 准教授 (10370983)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 統合失調症 / ＧＷＡＳ / 認知機能障害 / 分子遺伝機構 / GWAS

Outline of Final Research Achievements

Cognitive impairments are a core feature in schizophrenia. These deficits could serve as effective tools for understanding the genetic architecture of schizophrenia. This study investigated whether genetic variants associated with cognitive impairments aggregate in functional gene networks related to the pathogenesis of schizophrenia. Genome-wide association studies (GWAS) of a range of cognitive phenotypes relevant to schizophrenia were performed in 400 healthy subjects. We attempted to replicate the GWAS data using 250 patients with schizophrenia and performed a meta-analysis of the GWAS finding and the replicated results. Gene-network analysis for genes in close proximity to the replicated variants was also performed. We found that genetic variants related to cognitive trait impairment in schizophrenia are involved in the N-Methyl-D-aspartate (NMDA) glutamate network.

Research Products

• [Journal Article] Glutamate Networks Implicate Cognitive Impairments in Schizophrenia: Genome-Wide Association Studies of 52 Cognitive Phenotypes. (2014)
  • Author(s): Ohi K, Hashimoto R, Ikeda M, Yamamori H, Yasuda Y, Fujimoto M, Umeda-Yano S, Fukunaga M, Fujino H, Watanabe Y, Iwase M, Kazui H, Iwata N, Weinberger DR, Takeda M.
  • Journal Title: Schizophr Bull. Volume: 41 Issue: 4 Pages: 909-18
  • DOI: 10.1093/schbul/sbu171
  • NAID: 40020682401
  • Peer Reviewed / Open Access
• [Presentation] 統合失調症の認知機能障害測定法及び治療プロトコールの開発ー個別化医療とバイオタイプ診断体系に向けてー (2016)
  • Author(s): 工藤紀子、住吉チカ、藤野陽生、田中萌子、奥田詩織、楠原一紗、池田学、藤本美智子、安田由華、山森英長、住吉太幹、橋本亮太
  • Organizer: 平成28年度AMED脳と心の研究課進捗報告会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-09
• [Remarks] 大阪大学大学院医学系研究科精神医学教室生物学的精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html
• [Remarks] 大阪大学大学院医学系研究科精神医学教室分子精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html