Abstract
BACKGROUND: Genome-wide association studies (GWAS) have identified hundreds of loci associated with alcohol-related traits. GWAS permit the calculation of polygenic risk scores (PRS), which aggregate genetic risk for a trait across the genome. To evaluate the usefulness of a PRS for problematic alcohol use (PAU)-which subsumes alcohol use disorder (AUD) and alcohol-related problems-we tested whether this PRS predicted heavy drinking and alcohol problems after accounting for family history of AUD and prior drinking history, robust and established predictors of PAU. METHODS: Participants (N=665) were European-ancestry members of the Michigan Longitudinal Study, a prospective family study with high rates (65%) of parental AUD. Participants reported their frequency of alcohol use, maximum drinks consumed in a 24-hour period, and alcohol use problems at four assessments in adolescence and young adulthood (11-29 years old). We used polygenic prediction via Bayesian regression and continuous shrinkage priors to create a PAU PRS using summary statistics from a meta-GWAS of PAU. RESULTS: After adjusting for demographic covariates, parental AUD, and drinking and alcohol use problems in early and mid/late adolescence, the PAU PRS was significantly associated with alcohol-related problems in young adulthood (β=.08, p=.047; R(2)=0.6%). The PAU PRS also had a significant indirect effect on alcohol use problems in young adulthood through earlier drinking and alcohol use problems (β=.02, p=.03). CONCLUSIONS: The PAU PRS predicted alcohol problems in young adulthood after accounting for parental history of AUD and alcohol use in adolescence, providing evidence that genetic data uniquely inform the etiology of alcohol problems.