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; Hong-Hee Won

doi:10.1038/s41562-025-02155-z

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^*
, Hong-Hee Won^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	2417
Pages (from-to)	1272-1282
Number of pages	11
Journal	Nature Human Behaviour
Volume	9
Issue number	6
Early online date	2025
DOIs	https://doi.org/10.1038/s41562-025-02155-z
Publication status	Published - Jun 2025

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Jung, J. Y., Ahn, Y., Park, J.-W., Jung, K., Kim, S., Lim, S., Jung, S.-H., Kim, H., Kim, B., Hwang, M. Y., Kim, Y. J., Park, W.-Y., Okbay, A., O’Connell, K. S., Andreassen, O. A., Myung, W., & Won, H.-H. (2025). Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation. Nature Human Behaviour, 9(6), 1272-1282. Article 2417. https://doi.org/10.1038/s41562-025-02155-z

@article{0eca474f813041de9635f89e891bc0bf,

title = "Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation",

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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2025.",

year = "2025",

month = jun,

doi = "10.1038/s41562-025-02155-z",

language = "English",

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Jung, JY, Ahn, Y, Park, J-W, Jung, K, Kim, S, Lim, S, Jung, S-H, Kim, H, Kim, B, Hwang, MY, Kim, YJ, Park, W-Y, Okbay, A, O’Connell, KS, Andreassen, OA, Myung, W & Won, H-H 2025, 'Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation', Nature Human Behaviour, vol. 9, no. 6, 2417, pp. 1272-1282. https://doi.org/10.1038/s41562-025-02155-z

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T1 - Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation

AU - Jung, Jin Young

AU - Ahn, Yeeun

AU - Park, Jung-Wook

AU - Jung, Kyeongmin

AU - Kim, Soyeon

AU - Lim, Soohyun

AU - Jung, Sang-Hyuk

AU - Kim, Hyejin

AU - Kim, Beomsu

AU - Hwang, Mi Yeong

AU - Kim, Young Jin

AU - Park, Woong-Yang

AU - Okbay, Aysu

AU - O’Connell, Kevin S.

AU - Andreassen, Ole A.

AU - Myung, Woojae

AU - Won, Hong-Hee

PY - 2025/6

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AB - 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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JO - Nature Human Behaviour

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

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