Neuropsychiatric polygenic scores are weak predictors of professional categories

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 and Panos Roussos ()
Additional contact information
Georgios Voloudakis: JJ Peters VA Medical Center
Karen Therrien: JJ Peters VA Medical Center
Simone Tomasi: JJ Peters VA Medical Center
Veera M. Rajagopal: Aarhus University
Shing Wan Choi: Icahn School of Medicine at Mount Sinai
Ditte Demontis: Aarhus University
John F. Fullard: Icahn School of Medicine at Mount Sinai
Anders D. Børglum: Aarhus University
Paul F. O’Reilly: Icahn School of Medicine at Mount Sinai
Gabriel E. Hoffman: JJ Peters VA Medical Center
Panos Roussos: JJ Peters VA Medical Center

Nature Human Behaviour, 2025, vol. 9, issue 3, 595-608

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41562-024-02074-5

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