Voloudakis Georgios, Therrien Karen, Tomasi Simone, Rajagopal Veera M, Choi Shing Wan, Demontis Ditte, Fullard John F, Børglum Anders D, O'Reilly Paul F, Hoffman Gabriel E, Roussos Panos
Center for Precision Medicine and Translational Therapeutics, JJ Peters VA Medical Center, Bronx, NY, USA.
Mental Illness Research Education and Clinical Center, JJ Peters VA Medical Center, Bronx, NY, USA.
Nat Hum Behav. 2025 Mar;9(3):595-608. doi: 10.1038/s41562-024-02074-5. Epub 2024 Dec 10.
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.
多基因评分（PGS）有助于探索多效性效应和对复杂性状进行基因组剖析。在此，我们对来自百万退伍军人计划和英国生物银行的421889名欧洲血统个体进行研究，考察17种神经精神性状的PGS与22个广泛职业类别的归属之间的关系。总体而言，我们发现大多数职业类别与至少一种神经精神性状的遗传易感性之间存在统计学上显著但微弱的关联（每个PGS标准差的最高优势比为1.1）。在英国生物银行进行的二次分析显示，这些关联独立于观察到的流体智力和性别特异性效应。通过利用总体人群趋势，我们发现了符合公共利益的模式，比如受教育程度在注意力缺陷多动障碍PGS与多个职业类别之间的关联中所起的中介作用。然而，在个体层面，PGS对职业归属差异的解释不到0.5%，在我们对教育和社会经济地位进行调整后，几乎没有解释力。
