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

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 () and Hong-Hee Won ()
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Jin Young Jung: Sungkyunkwan University, Samsung Medical Center
Yeeun Ahn: Sungkyunkwan University, Samsung Medical Center
Jung-Wook Park: Sungkyunkwan University, Samsung Medical Center
Kyeongmin Jung: Sungkyunkwan University, Samsung Medical Center
Soyeon Kim: Sungkyunkwan University, Samsung Medical Center
Soohyun Lim: Sungkyunkwan University
Sang-Hyuk Jung: Kangwon National University College of Medicine
Hyejin Kim: Sungkyunkwan University, Samsung Medical Center
Beomsu Kim: Sungkyunkwan University, Samsung Medical Center
Mi Yeong Hwang: National Institute of Health
Young Jin Kim: National Institute of Health
Woong-Yang Park: Sungkyunkwan University School of Medicine
Aysu Okbay: Vrije Universiteit Amsterdam
Kevin S. O’Connell: Oslo University Hospital
Ole A. Andreassen: Oslo University Hospital
Woojae Myung: Seoul National University Bundang Hospital
Hong-Hee Won: Sungkyunkwan University, Samsung Medical Center

Nature Human Behaviour, 2025, vol. 9, issue 6, 1272-1282

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41562-025-02155-z

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