Searching for risk genes for schizophrenia based on a whole-exome sequencing of a consanguineous family with affected siblings

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19754
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Niigata University
• Principal Investigator: Igeta Hirofumi 新潟大学, 医歯学総合研究科, 非常勤講師 (10751026)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 精神医学 / 分子遺伝学 / 統合失調症 / エクソーム解析

Outline of Final Research Achievements

Whole-exome sequencing (WES) studies of multiplex families are likely be a promising strategy for identifying causative variations for common diseases. We performed a WES study in two affected siblings and their unaffected parents who were second cousins from a multiplex schizophrenia family. Potential risk variations prioritized via WES were further tested for associations with schizophrenia in a total of 2,837 patients and 3,951 controls.
Via WES, we identified two uncommon homozygous recessive missense variations, p.Arg140Gln in HEBP2 and p.Arg152Cys in UPK2, shared by two affected siblings. In a case-control study, these variations were not significantly associated with schizophrenia, although there was only one homozygous mutant allele carrier of p.Arg152Cys in UPK2 in patients, but not in controls.
Our data do not support the role of p.Arg140Gln in HEBP2 and p.Arg152Cys in UPK2 in conferring substantial risk for schizophrenia in the Japanese population.

Free Research Field

分子遺伝学