The impact of assortative mating, participation bias, and socioeconomic status on the polygenic risk of behavioral and psychiatric traits

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.