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. 2025 Jun;9(6):1272-1282.
doi: 10.1038/s41562-025-02155-z. Epub 2025 Apr 14.

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

Jin Young Jung  1   2 , Yeeun Ahn  1 , Jung-Wook Park  1 , Kyeongmin Jung  1   3 , Soyeon Kim  1 , Soohyun Lim  4 , Sang-Hyuk Jung  5 , Hyejin Kim  1 , Beomsu Kim  1 , Mi Yeong Hwang  6 , Young Jin Kim  6 , Woong-Yang Park  7 , Aysu Okbay  8 , Kevin S O'Connell  9 , Ole A Andreassen  9 , Woojae Myung #  10   11 , Hong-Hee Won #  12   13
Affiliations

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

Jin Young Jung et al. Nat Hum Behav. 2025 Jun.

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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Conflict of interest statement

Competing interests: W.-Y.P. is employed by the commercial company GENINUS. O.A.A. is a consultant for HealthLytix and cortecs.ai; he has received speaker’s honoraria from Janssen, Sunovion, and Lundbeck. The remaining authors declare no competing interests.

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