Abstract
To investigate assortative mating (AM), participation bias, and socioeconomic status (SES) with respect to the genetics of behavioral and psychiatric traits, we analyzed gametic phase disequilibrium (GPD), within-spouses and within-siblings polygenic risk score (PRS) correlation, performing a SES conditional analysis. We observed genetic signatures of AM across multiple methods for traits related to substance use with SES conditioning increasing the within-spouses PRS correlation for Frequency of drinking alcohol (2.5% to 6%), Maximum habitual alcohol intake (1.33% to 4.43%), and Ever taken cannabis (1.5% to 5.3%). Comparing UK Biobank mental health questionnaire responders vs. non-responders, major depressive disorder PRS showed significant GPD in both groups when based on the Million Veteran Program (3.2% vs. 3%), but only in responders when based on the Psychiatric Genomics Consortium (3.8% vs. 0.2%). These results highlight the impact of AM, participation bias, and SES on the polygenic risk of behavioral and psychiatric traits.
Competing Interest Statement
Dr. Polimanti is paid for their editorial work on the journal Complex Psychiatry and reports a research grant from Alkermes. The other authors declare no competing interests.
Funding Statement
The authors acknowledge support from the National Institutes of Health (R21 DC018098, R33 DA047527, RF1 MH132337, and K99 AG078503), One Mind, and the American Foundation for Suicide Prevention (PDF-1-022-21).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
All GWAS data are publicly available on their respective websites. UK Biobank, https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access Psychiatric Genomics Consortium, https://pgc.unc.edu/for-researchers/download-results/ Million Veteran Program, https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001672.v8.p1
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Data Availability
All results used to make conclusions discussed in this study are provided as Supplementary Material.