Rare gene variations and risk of schizophrenia: whole-exome sequencing in families with affected siblings followed by targeted resequencing and a case-control study

Research Project

Project/Area Number	15K19716
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Psychiatric science
Research Institution	Niigata University
Principal Investigator	HOYA Satoshi 新潟大学, 医歯学総合研究科, 非常勤講師 (50748580)
Project Period (FY)	2015-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords	統合失調症 / 罹患同胞対 / 全エクソーム解析 / PDCD11遺伝子 / 日本人 / エクソーム解析
Outline of Final Research Achievements	To identify rare variations that have strong impact on the risk of developing schizophrenia, we performed a three-stage study. In the first stage, we identified two rare missense PDCD11 variations (D961N and V1240L) using whole-exome sequencing (WES) data from three families, each with two affected siblings. In the second stage, we identified three rare non-synonymous variations (V1240L, F1835del, and R1837H) via targeted resequencing of the PDCD11 coding region in 96 patients. In the third stage, a case-control study demonstrated no significant associations between schizophrenia and four rare PDCD11 variations in a total of 1,357 patients and 1,394 controls. Our data do not support the role of rare PDCD11 variations in conferring substantial risk for schizophrenia in the Japanese population.