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

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  • Jin Young Jung

    (Sungkyunkwan University, Samsung Medical Center
    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
    Seoul National University Bundang Hospital)

  • 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
    Seoul National University, College of Medicine)

  • Hong-Hee Won

    (Sungkyunkwan University, Samsung Medical Center
    National Institute of Health)

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.

Suggested Citation

  • 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 & Kev, 2025. "Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation," Nature Human Behaviour, Nature, vol. 9(6), pages 1272-1282, June.
    • Handle: RePEc:nat:nathum:v:9:y:2025:i:6:d:10.1038_s41562-025-02155-z
    DOI: 10.1038/s41562-025-02155-z
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