Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation

IF 21.4 1区心理学 Q1 MULTIDISCIPLINARY SCIENCES

Nature Human Behaviour Pub Date : 2025-04-14 DOI:10.1038/s41562-025-02155-z

Jin Young Jung, Yeeun Ahn, Jung-Wook Park, Kyeongmin Jung, Soyeon Kim, Soohyun Lim, Sang-Hyuk Jung, Hyejin Kim, Beomsu Kim, Mi Yeong Hwang, Young Jin Kim , Woong-Yang Park, Aysu Okbay, Kevin S. O’Connell, Ole A. Andreassen, Woojae Myung, Hong-Hee Won

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Abstract

Subjective well-being (SWB) is important for understanding human behaviour and health. Although the connection between SWB and psychiatric disorders has been studied, common genetic mechanisms remain unclear. This study aimed to explore the genetic relationship between SWB and psychiatric disorders. Bivariate causal mixture modelling (MiXeR), polygenic risk score (PRS) and Mendelian randomization (MR) analyses showed substantial polygenic overlap and associations between SWB and the psychiatric disorders. Subsequent replication studies in East Asian populations confirmed the polygenic overlap between schizophrenia and SWB. The conditional and conjunctional false discovery rate analyses identified additional or shared genetic loci associated with SWB or psychiatric disorders. Functional annotation revealed enrichment of specific brain tissues and genes associated with SWB. The identified genetic loci showed cross-ancestry transferability between the European and Korean populations. Our findings provide valuable insights into the common genetic mechanisms underlying SWB and psychiatric disorders.

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主观幸福感与精神疾病的多基因重叠及跨祖先验证

主观幸福感（SWB）对于理解人类行为和健康非常重要。虽然SWB和精神疾病之间的联系已被研究，但共同的遗传机制仍不清楚。本研究旨在探讨主观幸福感与精神疾病的遗传关系。双变量因果混合模型（MiXeR）、多基因风险评分（PRS）和孟德尔随机化（MR）分析显示，SWB和精神疾病之间存在大量的多基因重叠和关联。随后在东亚人群中的复制研究证实了精神分裂症和SWB之间的多基因重叠。条件和联合错误发现率分析确定了与SWB或精神疾病相关的额外或共享遗传位点。功能注释显示特异性脑组织和SWB相关基因的富集。所鉴定的遗传位点显示出欧洲和韩国人群之间的跨祖先可转移性。我们的发现为SWB和精神疾病的共同遗传机制提供了有价值的见解。

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来源期刊

Nature Human Behaviour Psychology-Social Psychology

CiteScore

36.80

自引率

1.00%

发文量

227

期刊介绍： Nature Human Behaviour is a journal that focuses on publishing research of outstanding significance into any aspect of human behavior.The research can cover various areas such as psychological, biological, and social bases of human behavior.It also includes the study of origins, development, and disorders related to human behavior.The primary aim of the journal is to increase the visibility of research in the field and enhance its societal reach and impact.