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Neuropsychiatric polygenic scores are weak predictors of professional categories

Author

Listed:
  • Georgios Voloudakis

    (JJ Peters VA Medical Center
    JJ Peters VA Medical Center
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Karen Therrien

    (JJ Peters VA Medical Center
    JJ Peters VA Medical Center
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Simone Tomasi

    (JJ Peters VA Medical Center
    JJ Peters VA Medical Center
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Veera M. Rajagopal

    (Aarhus University
    iPSYCH
    Center for Genomics and Personalized Medicine
    Regeneron Genetics Center)

  • Shing Wan Choi

    (Icahn School of Medicine at Mount Sinai)

  • Ditte Demontis

    (Aarhus University
    iPSYCH
    Center for Genomics and Personalized Medicine)

  • John F. Fullard

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Anders D. Børglum

    (Aarhus University
    iPSYCH
    Center for Genomics and Personalized Medicine)

  • Paul F. O’Reilly

    (Icahn School of Medicine at Mount Sinai)

  • Gabriel E. Hoffman

    (JJ Peters VA Medical Center
    JJ Peters VA Medical Center
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Panos Roussos

    (JJ Peters VA Medical Center
    JJ Peters VA Medical Center
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

Polygenic scores (PGS) enable the exploration of pleiotropic effects and genomic dissection of complex traits. Here, in 421,889 individuals with European ancestry from the Million Veteran Program and UK Biobank, we examine how PGS of 17 neuropsychiatric traits are related to membership in 22 broad professional categories. Overall, we find statistically significant but weak (the highest odds ratio is 1.1 per PGS standard deviation) associations between most professional categories and genetic predisposition for at least one neuropsychiatric trait. Secondary analyses in UK Biobank revealed independence of these associations from observed fluid intelligence and sex-specific effects. By leveraging aggregate population trends, we identified patterns in the public interest, such as the mediating effect of education attainment on the association of attention-deficit/hyperactivity disorder PGS with multiple professional categories. However, at the individual level, PGS explained less than 0.5% of the variance of professional membership, and almost none after we adjusted for education and socio-economic status.

Suggested Citation

  • Georgios Voloudakis & Karen Therrien & Simone Tomasi & Veera M. Rajagopal & Shing Wan Choi & Ditte Demontis & John F. Fullard & Anders D. Børglum & Paul F. O’Reilly & Gabriel E. Hoffman & Panos Rousso, 2025. "Neuropsychiatric polygenic scores are weak predictors of professional categories," Nature Human Behaviour, Nature, vol. 9(3), pages 595-608, March.
    • Handle: RePEc:nat:nathum:v:9:y:2025:i:3:d:10.1038_s41562-024-02074-5
    DOI: 10.1038/s41562-024-02074-5
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