Novel hypothesis for pathophysiology of schizophrenia based on its genetic architectures

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05378
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Fujita Health University
• Principal Investigator: Iwata Nakao 藤田医科大学, 医学部, 教授 (60312112)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 精神科遺伝学

Outline of Final Research Achievements

Genetic architecture of schizophrenia remains largely unknown, although Genome-wide association study (GWAS) has contributed for detecting pathophysiology of complex disorders. One of the reasons is that most studies are conducted based on “separate analysis” between common polymorphism (single nucleotide polymorphism: SNP) and rare variant (copy number variant: CNV), so far. In this study, we conducted a joint analysis merging SNP (and polygenic risk score calculated by whole-genome SNP effect) and CNV. Here, we detected the possible “genuine” CNVs were enriched in the lower PRS which had lower risk for schizophrenia based on polygenic model. Further study will be required to obtain conclusive results, however, such hybrid analysis will be essential for schizophrenia.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

CNVを始めとする稀な変異のリスクを統計的に証明することは検出力の観点から極めて困難である。そのため、リスクとなりうるCNVの重み付けをつけることは、膨大なCNVの機能を解明していく上で、一定の優先順位を与えることとなり、極めて有用な情報を与えうる。すなわち、本方法論を用いれば、統計的には有意でなくとも、ポリジェニックスコアの低い患者は、リスクとなりうる稀でかつ効果の大きい変異を持つ可能性があり、その変異自体の機能解析を実施する指針を与えうる。