Genetic risk for alcohol problems was indexed using genome-wide polygenic scores (PRS). Genome-wide PRS represents the state of the science approach to index an individual’s overall genetic liability for a given trait/behavior using molecular genetic data (Wray et al., 2014). This approach uses the results from a genome-wide association study (GWAS) in a large-scale gene identification discovery sample to calculate a personalized measure of genetic risk for individuals in a target sample. A polygenic score is calculated by summing over the number of alleles for each single nucleotide polymorphism (SNP), weighted by the effect size drawn from a GWAS. Thus, a PRS is a weighted sum of risk-increasing alleles that an individual carries across their genome (for more extensive reviews, see Bogdan et al., 2018). We used PRS-CS “auto” (Ge et al., 2019) to calculate an alcohol problems PRS. This approach employs a Bayesian regression and continuous shrinkage method to correct for the non-independence among nearby SNPs in the genome.
