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Shared genetic architectures of subjective well-being in East Asian and European ancestry populations

Nature Human Behaviour volume 6, pages 1014–1026 (2022)Cite this article

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Abstract

Subjective well-being (SWB) has been explored in European ancestral populations; however, whether the SWB genetic architecture is shared across populations remains unclear. We conducted a cross-population genome-wide association study for SWB using samples from Korean (n = 110,919) and European (n = 563,176) ancestries. Five ancestry-specific loci and twelve cross-ancestry significant genomic loci were identified. One novel locus (rs12298541 near HMGA2) associated with SWB was also identified through the European meta-analysis. Significant cross-ancestry genetic correlation for SWB between samples was observed. Polygenic risk analysis in an independent Korean cohort (n = 22,455) demonstrated transferability between populations. Significant correlations between SWB and major depressive disorder, and significant enrichment of central nervous system-related polymorphisms heritability in both ancestry populations were found. Hence, large-scale cross-ancestry genome-wide association studies can advance our understanding of SWB genetic architecture and mental health.

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Fig. 1: Genetic association of SWB in samples of Korean and European ancestries.
Fig. 2: Effect sizes for SWB in populations of Korean and European ancestries.
Fig. 3: Polygenic risk prediction in an independent Korean cohort based on Korean GWAS and meta-analysis results for samples of Korean and European ancestries.
Fig. 4: Genetic correlations between SWB from the European meta-analysis and other traits from publicly available GWAS summary statistics of European ancestry.
Fig. 5: Results of the multiple-tissue analysis for SWB.

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Data availability

Data from the UKB and 23andMe are available on application to each site (UKB, https://www.ukbiobank.ac.uk; 23andMe, https://research.23andme.com/dataset-access/). Summary statistics of Okbay and colleagues7 are publicly available at the Social Science Genetic Association Consortium (SSGAC, https://www.thessgac.org/). The full summary statistics of the KBA GWAS are available at the NHGRI-EBI GWAS Catalog (https://www.ebi.ac.uk/gwas/downloads).

Code availability

Previously developed pipelines were used to produce the results for the current study. No custom code was developed. Please see the Supplementary Information for details on the software URLs and data used.

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Acknowledgements

KBA genotype data were provided by the Collaborative Genome Program for Fostering New Post-Genome Industry (3000–3031b), and UKB data were obtained under application no. 33002. This study was supported by the National Research Foundation of Korea Grant funded by the Ministry of Science and Information and Communication Technologies, South Korea (grant no. NRF‐2018R1C1B6001708 and NRF-2021R1A2C4001779 to W.M. and NRF-2019R1A2C4070496 and NRF-2022R1A2C2009998 to H.H.W.) and by an intramural grant from the Korea National Institute of Health (2019-NG-053-01). This research was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant nos. HI19C1132 and HI19C1328000020 to H.H.W. and S.K., respectively). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Author notes

  1. These authors contributed equally: Soyeon Kim, Kiwon Kim, Mi Yeong Hwang.

  2. These authors jointly supervised this work: Young Jin Kim, Woojae Myung, Hong-Hee Won.

Authors and Affiliations

  1. Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea

    Soyeon Kim, Sang-Hyuk Jung, Injeong Shim, Soojin Cha, Beomsu Kim & Hong-Hee Won

  2. Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea

    Soyeon Kim, Joohyun Yoon, Tae Hyon Ha & Woojae Myung

  3. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Soyeon Kim

  4. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Soyeon Kim

  5. Department of Psychiatry, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea

    Kiwon Kim

  6. Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, Chungcheongbuk-do, South Korea

    Mi Yeong Hwang, Bong-Jo Kim & Young Jin Kim

  7. Interdisciplinary Program in Cognitive Science, Seoul National University, Seoul, South Korea

    Hyunwoong Ko

  8. Department of Health Administration and Management, College of Medical Sciences, Soonchunhyang University, Asan-si, Chungcheongnam-do, South Korea

    Hyewon Lee

  9. Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Doh Kwan Kim

  10. Precision Medicine Center, Future Innovation Research Division, Seoul National University Bundang Hospital, Seongnam, South Korea

    Jinho Kim

  11. Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Woong-Yang Park & Hong-Hee Won

  12. Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    Aysu Okbay

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Contributions

H.H.W., W.M. and Y.J.K. had full access to all data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. S.K., K.K., H.H.W. and W.M. conceived and designed the study. S.K., M.Y.H. and H.H.W. performed the statistical analyses. S.K., K.K., M.Y.H., H.H.W., W.M. and Y.J.K. drafted the manuscript. H.H.W., W.M. and Y.J.K. supervised the entire study. All authors contributed to the interpretation of the data and have read and approved the final draft for submission. S.K., K.K. and M.Y.H. contributed equally to this work. H.H.W., W.M. and Y.J.K. jointly supervised this work.

Corresponding authors

Correspondence to Young Jin Kim, Woojae Myung or Hong-Hee Won.

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Woong-Yang Park is employed by a commercial company, GENINUS. GENINUS has no particular conflict of interest with the current work. The remaining authors declare no competing interests.

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Nature Human Behaviour thanks Michelle Luciano and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Kim, S., Kim, K., Hwang, M.Y. et al. Shared genetic architectures of subjective well-being in East Asian and European ancestry populations. Nat Hum Behav 6, 1014–1026 (2022). https://doi.org/10.1038/s41562-022-01343-5

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