Comprehensive analysis of splicing regulation and splicing quantitative trait loci (sQTL) in brains of major psychoses

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H06254
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Yokohama City University
• Principal Investigator: Takata Atsushi 横浜市立大学, 医学部, 講師 (90643693)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 選択的スプライシング / ゲノム / 統合失調症

Outline of Final Research Achievements

In this program, we conducted a comprehensive analysis of association between alternative splicing and neuropsychiatric disorders. Specifically, we reported the results of genome-wide identification of splicing quantitative trait loci (sQTLs) in the human brain and analysis of their association with neuropsychiatric disorders such as schizophrenia (Takata et al., Nature Communications 2017), and large-scale exome studies of autism spectrum disorder and developmental and epileptic encephalopathy analyzing rare variants including those potentially affect alternative splicing (Takata et al., Cell Reports 2018, Takata et al., Nature Communications 2019).

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

本研究で作製した、選択的スプライシングに影響を及ぼす変異の網羅的カタログは、ゲノムワイド関連解析等で検出される疾患関連SNPの生物学的意義の解釈と、疾患メカニズム解明に活用することができる。また、エクソーム解析等の網羅的ゲノム解析において、選択的スプライシング影響する変異を考慮することで、遺伝子診断につながる病的変異や、疾患リスクに寄与する変異を同定できる確率の向上が見込める。これらはいずれも、精神神経疾患のゲノム・脳病態理解と、診断・予防・将来の治療法開発に貢献しうるものである。