Contributions of an Internalizing Symptoms Polygenic Risk Score and Contextual Factors to Alcohol-Related Disorders in African American Young Adults

Objective: Alcohol-related disorders (i.e., abuse and dependence) are significant problems that may result in numerous negative consequences. Although a number of studies have examined factors that predict alcohol abuse and dependence in European samples. only a few studies have examined whether genetic and environmental factors influence the pathogenesis of alcohol-related disorders among African Americans. The present study examined whether gene (internalizing symptoms polygenic risk score) by environment (parental monitoring, community disadvantage) interactions were associated with alcohol-related disorders in a sample of African American adults. Method: Participants (N= 640; 39.7% male) were initially recruited for an elementary school-based universal prevention trial in a mid-Atlantic city and followed into adulthood. Participants reported on their perceptions of parental monitoring in sixth grade. At 30 years of age, participants reported on their alcohol abuse and dependence, and DNA was obtained and genotyped using Affymetrix 6.0 microarrays. An internalizing symptoms polygenic risk score was created using discovery samples results from a genome-wide association study (GWAS) that involved three large population-based studies. Community disadvantage was calculated based on census data when participants were in first grade. Results: There was a significant interaction between the internalizing symptoms polygenic risk score and community disadvantage such that exposure to higher community disadvantage was associated with lower risk for alcohol-related disorders among participants with a higher internalizing symptoms polygenic risk score. Conclusions: Our findings highlight that higher genetic loading for internalizing symptoms may protect urban African Americans from alcohol-related disorders, particularly in more disadvantaged areas.