Neuropsychiatric Polygenic Scores Are Weak Predictors of Professional Categories

Overview

Journal Nat Hum Behav

Specialties Psychology
Social Sciences

Date 2024 Dec 10

PMID 39658624

Authors

Georgios Voloudakis

Karen Therrien

Simone Tomasi

Veera M Rajagopal

Shing Wan Choi

Ditte Demontis

John F Fullard

Anders D Borglum

Paul F OReilly

Gabriel E Hoffman

Panos Roussos

Affiliations

Soon will be listed here.

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.

References

Hatemi P, Medland S, Klemmensen R, Oskarsson S, Littvay L, Dawes C . Genetic influences on political ideologies: twin analyses of 19 measures of political ideologies from five democracies and genome-wide findings from three populations. Behav Genet. 2014; 44(3):282-94. PMC: 4038932. DOI: 10.1007/s10519-014-9648-8. View

Hatemi P, McDermott R . The genetics of politics: discovery, challenges, and progress. Trends Genet. 2012; 28(10):525-33. DOI: 10.1016/j.tig.2012.07.004. View

Abdellaoui A, Hugh-Jones D, Yengo L, Kemper K, Nivard M, Veul L . Genetic correlates of social stratification in Great Britain. Nat Hum Behav. 2019; 3(12):1332-1342. DOI: 10.1038/s41562-019-0757-5. View

Day F, Ong K, Perry J . Elucidating the genetic basis of social interaction and isolation. Nat Commun. 2018; 9(1):2457. PMC: 6030100. DOI: 10.1038/s41467-018-04930-1. View

Okbay A, Beauchamp J, Fontana M, Lee J, Pers T, Rietveld C . Genome-wide association study identifies 74 loci associated with educational attainment. Nature. 2016; 533(7604):539-42. PMC: 4883595. DOI: 10.1038/nature17671. View

Lee J, Wedow R, Okbay A, Kong E, Maghzian O, Zacher M . Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nat Genet. 2018; 50(8):1112-1121. PMC: 6393768. DOI: 10.1038/s41588-018-0147-3. View

Rietveld C, Medland S, Derringer J, Yang J, Esko T, Martin N . GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. Science. 2013; 340(6139):1467-71. PMC: 3751588. DOI: 10.1126/science.1235488. View

Belsky D, Moffitt T, Corcoran D, Domingue B, Harrington H, Hogan S . The Genetics of Success: How Single-Nucleotide Polymorphisms Associated With Educational Attainment Relate to Life-Course Development. Psychol Sci. 2016; 27(7):957-72. PMC: 4946990. DOI: 10.1177/0956797616643070. View

Li H, Zhang C, Cai X, Wang L, Luo F, Ma Y . Genome-wide Association Study of Creativity Reveals Genetic Overlap With Psychiatric Disorders, Risk Tolerance, and Risky Behaviors. Schizophr Bull. 2020; 46(5):1317-1326. PMC: 7505179. DOI: 10.1093/schbul/sbaa025. View

10.

Hill W, Davies N, Ritchie S, Skene N, Bryois J, Bell S . Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income. Nat Commun. 2019; 10(1):5741. PMC: 6915786. DOI: 10.1038/s41467-019-13585-5. View

11.

Vreeker A, Boks M, Abramovic L, Verkooijen S, van Bergen A, Hillegers M . High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls. Psychol Med. 2015; 46(4):807-18. PMC: 5824688. DOI: 10.1017/S0033291715002299. View

12.

Bansal V, Mitjans M, Burik C, Linner R, Okbay A, Rietveld C . Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia. Nat Commun. 2018; 9(1):3078. PMC: 6079028. DOI: 10.1038/s41467-018-05510-z. View

13.

Dalsgaard S, McGrath J, Ostergaard S, Wray N, Pedersen C, Mortensen P . Association of Mental Disorder in Childhood and Adolescence With Subsequent Educational Achievement. JAMA Psychiatry. 2020; 77(8):797-805. PMC: 7097843. DOI: 10.1001/jamapsychiatry.2020.0217. View

14.

MacCabe J, Sariaslan A, Almqvist C, Lichtenstein P, Larsson H, Kyaga S . Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case-control study and sib-pair analysis. Br J Psychiatry. 2018; 212(6):370-376. DOI: 10.1192/bjp.2018.23. View

15.

Parnas J, Sandsten K, Vestergaard C, Nordgaard J . Schizophrenia and Bipolar Illness in the Relatives of University Scientists: An Epidemiological Report on the Creativity-Psychopathology Relationship. Front Psychiatry. 2019; 10:175. PMC: 6454109. DOI: 10.3389/fpsyt.2019.00175. View

16.

Burstein D, Griffen T, Therrien K, Bendl J, Venkatesh S, Dong P . Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism. Nat Genet. 2023; 55(9):1462-1470. PMC: 10947608. DOI: 10.1038/s41588-023-01464-1. View

17.

Bigdeli T, Voloudakis G, Barr P, Gorman B, Genovese G, Peterson R . Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System. JAMA Psychiatry. 2022; . PMC: 9475441. DOI: 10.1001/jamapsychiatry.2022.2742. View

18.

Demontis D, Walters G, Athanasiadis G, Walters R, Therrien K, Nielsen T . Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Nat Genet. 2023; 55(2):198-208. PMC: 10914347. DOI: 10.1038/s41588-022-01285-8. View

19.

Zheutlin A, Dennis J, Linner R, Moscati A, Restrepo N, Straub P . Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems. Am J Psychiatry. 2019; 176(10):846-855. PMC: 6961974. DOI: 10.1176/appi.ajp.2019.18091085. View

20.

Hingorani A, Gratton J, Finan C, Schmidt A, Patel R, Sofat R . Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog. BMJ Med. 2023; 2(1):e000554. PMC: 10582890. DOI: 10.1136/bmjmed-2023-000554. View