JCAD and SLC39A13. More recently, 18 genome-wide significant loci were identified in a GWAS of alcohol use disorder from the Million Veteran Program [6]. Forthcoming findings from even larger consortia-based efforts will be highly informative for gene discovery regarding alcohol use behavior and AUD. However, GWAS represents only the beginning of our understanding of genomic influences on AUD. Deeply phenotyped samples are needed to characterize results emerging from their findings, particularly with respect to brain function, which might serve as a pathway for genetic vulnerability for AUD to be expressed. Polygenic risk scores (PRS) aggregate genetic information from GWAS [9], permitting studies of aggregated risk in independent samples. Briefly, PRS represent an individual’s genetic liability for a trait or disorder such as alcohol dependence, created by summing the effect sizes (from a GWAS) of many risk variants for the phenotype of interest, weighted by the number of effect alleles in individual carriers at each locus. By harnessing the well-known and massive polygenicity underlying AUD, PRS can be used to enhance our understanding of how genetic vulnerability to AUD is reflected in neural connectivity, among other aspects of brain activity, and thus provide important context to findings emerging from these large-scale
