Psychiatric and substance use disorder polygenic scores are associated with the exposome in youth

Gene-environment correlations (rGE) present challenges for accurately estimating the individual and joint contributions of genetic and environmental influences on risk for psychiatric and substance use disorders. The present study examined rGE between polygenic risk scores (PGS) for psychiatric and substance use disorders and environmental exposures (i.e., exposome factors) using multi-level data spanning youth- and parent-reports, as well as objective measures of the built environment. Participants included 4,797 genetically similar to European reference populations, 1,585 genetically similar to African reference populations, and 2,012 genetically similar to Admixed American reference populations from the Adolescent Brain and Cognitive Development (ABCD) Study. The ABCD study was conducted at 21 sites across the U.S and used a stratified probability sampling design to ensure the cohort recruited was demographically diverse. Based on factor-analytic work conducted by Moore et al. (2022) in the ABCD study, the exposome included 6 factors: household adversity, neighborhood adversity, positive day-to-day experiences, state conservatism/ruralness, family values, and pregnancy/birth complications. Disorder-specific PGS for psychiatric (e.g., major depressive disorder, attention deficit hyperactivity disorder) and substance use conditions (e.g., alcohol use disorders, cannabis use disorders), as well as PGS for common liability for externalizing and general substance use disorders, were used to examine genetic associations with the exposome factors. After adjusting for participant sex, age, log income-to-needs ratio, and genetic ancestry principal components, higher PGS for psychiatric (e.g., broad externalizing liability, attention deficit hyperactivity disorder) and substance use disorders (e.g., general substance use disorders, cannabis use disorder) were positively associated with household adversity and negatively associated with positive day-to-day experiences. Our results indicate that polygenic risk for psychiatric and substance use disorders correlate with environmental factors in adolescence at multiple levels, most notably household adversity and positive day-to-day experiences. Findings underscore the importance of investigating rGE when examining these environmental exposures with genetic risk for psychiatric and substance use disorders.