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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Data availability
Data from 23andMe Inc. and UKB can be obtained by applying to each respective website (23andMe Inc., https://research.23andme.com/dataset-access/; UKB, https://www.ukbiobank.ac.uk). Summary statistics from ref. 4 are publicly accessible on the Social Science Genetic Association Consortium website (https://www.thessgac.org). Summary statistics for genetic correlation analysis are available from various sources, including the Psychiatric Genomics Consortium (https://www.med.unc.edu/pgc/download-results), GWAS ATLAS (https://atlas.ctglab.nl/traitDB) and GWAS Catalogue (https://www.ebi.ac.uk/gwas/studies). Full summary statistics of the KBA GWAS can be found in the NHGRI-EBI GWAS Catalogue (https://www.ebi.ac.uk/gwas/downloads).
Code availability
In this study, existing pipelines were utilized to obtain the results, and no new code was created. Further information regarding the software and data utilization can be found in Supplementary Information, including the URLs. The protocol and specific details of our MR analyses were not registered in advance.
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Acknowledgements
This study was conducted using bioresources from the National Biobank of Korea at the Korea Disease Control and Prevention Agency, South Korea (KBN-2021-031). This study was supported by grants from the National Research Foundation of Korea funded by the Ministry of Science and Information and Communication Technologies, South Korea (Grant Nos. NRF-2021R1A2C4001779 and RS-2024-00335261 to W.M. and NRF-2022R1A2C2009998 to H.-H.W.); the NAVER Digital Bio Innovation Research Fund, funded by NAVER Corporation (Grant No. 37-2023-0140); and by an MD-PhD/Medical Scientist Training Program grant from the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HC20C0005).
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W.M. and H.-H.W. had full access to all data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. J.Y.J., W.M. and H.-H.W. conceived and designed the study. J.Y.J., Y.A. and J.-W.P. performed the statistical analyses. J.Y.J., Y.A., J.-W.P. and S.L. drafted the manuscript. K.S.O., O.A.A., W.M. and H.-H.W. supervised the study and critically revised the manuscript. All authors including K.J., S.K., S.-H.J., H.K., B.K., M.Y.H., Y.J.K., W.-Y.P. and A.O. contributed to the data interpretation, writing of the manuscript, and reading and approval of the final draft for submission.
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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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Jung, J.Y., Ahn, Y., Park, JW. et al. Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation. Nat Hum Behav 9, 1272–1282 (2025). https://doi.org/10.1038/s41562-025-02155-z
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DOI: https://doi.org/10.1038/s41562-025-02155-z
