2023 Fiscal Year Final Research Report
Comprehensive investigation of rare germline and somatic mutations in bipolar disorder by large-scale sequencing analysis.
| Project/Area Number |
21H02855
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Takata Atsushi 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (90643693)
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| Co-Investigator(Kenkyū-buntansha) |
垣内 千尋 順天堂大学, 医学部, 先任准教授 (90342766)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | エクソーム / 双極性障害 / 双極症 / 体細胞変異 / 遺伝統計 |
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| Outline of Final Research Achievements |
We performed exome sequencing of bipolar disorder (BD) patients and conducted an integrated analysis with existing data. Our study of de novo variants detected by trio (proband and parents) sequencing revealed that both germline and somatic de novo variants contribute to the risk of BD. A more detailed analysis of somatic variants by deep exome sequencing showed that damaging somatic variants in genes where germline variants are known to cause neurodevelopmental and autistic spectrum disorders are significantly enriched in BD. In a large case-control analysis, we found that SETD1A, a gene known to be causally linked to schizophrenia and neurodevelopmental disorders, is also associated with BD.
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| Free Research Field |
精神医学・ゲノム医科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、慢性の経過を辿ることが多く、既存治療の有効性・安全性には限界があり、また根本病態は未解明な精神疾患である双極性障害（双極症）のゲノム解析を、稀な変異に焦点を当てて実施した。本研究の成果は、双極性障害の遺伝的構造（genetic architecture）の一端を新たに明らかにし、また他の精神疾患との遺伝的関連性についての理解を深めたという学術的意義を有するのみならず、疾患の病態理解、将来のゲノムプロファイルによるリスク予測、治療ターゲット同定などにつながりうるという点で社会的意義を有する。
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