• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2023 Fiscal Year Final Research Report

Phenome-wide association analysis and elucidation of the molecular basis of hypersomnia by Japanese-specific genetic variants

Research Project

  • PDF
Project/Area Number 21K07534
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KODAMA Tohru  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (20195746)

Co-Investigator(Kenkyū-buntansha) 宮川 卓  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 副参事研究員 (20512263)
嶋多 美穂子  国立研究開発法人国立国際医療研究センター, 研究所, ゲノム医科学プロジェクト 上級研究員 (50792727)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywords睡眠 / 特発性過眠症 / オレキシン / ゲノム / 変異 / ナルコレプシー / 東北メディカルメガバンク機構
Outline of Final Research Achievements

Association analyses were performed to identify genetics variants associated with idiopathic hypersomnia (IH). We found a significant association between IH and a rare missense variant located in the cleavage site of prepro-orexin gene (p.Lys68Arg). We confirmed that the association was replicated by a different sample set (IH and healthy control). Subjective sleepiness severity was higher in the orexin mutation-positive patients. Functional analyses of this missense variant revealed that the cleavage efficiency of the mutant allele was significantly lower and the non-cleaved form had significantly lower pharmacological activity. We conducted an association analysis genotype data and self-reported sleep data in Japanese individuals from the Tohoku Medical Megabank Project cohort. No significant association was observed between p.Lys68Arg and sleep phenotypes. However, a rare variant (rs188018846) located in orexin receptor-2 gene was significantly associated with daytime sleepiness.

Free Research Field

睡眠学

Academic Significance and Societal Importance of the Research Achievements

特発性過眠症はヘテロジニアスな疾患であり、その原因もほとんどわかっていない。本研究により、特発性過眠症や日中の眠気の原因の一つにオレキシンのパスウェイが関わることを明らかにした。オレキシンは睡眠覚醒制御に関わる神経ペプチドとして知られている。これまでナルコレプシーの発症にオレキシンが寄与すると考えられ、ナルコレプシー治療薬の重要なターゲットとされてきた。本研究の結果から、オレキシンが特発性過眠症の治療薬の候補ともなり得る。また、特発性過眠症や日中の眠気と関連した二つの変異は、どちらもヨーロッパ系集団やアフリカ系集団では、ほとんど認められない変異であり、集団特異的な解析の重要性も示唆された。

URL: 

Published: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi