In terms of which polygenic scores were the most predictive, we considered three scores: one based on problematic alcohol use (PROB ALC), one based on alcohol consumption (GSCAN DPW), and one based on general risky behaviors (RISK PC), as twin and family studies have shown alcohol and other risk behaviors to be genetically correlated traits6,14–18. In both samples, the GSCAN DPW PRS was the most strongly associated, followed closely by the RISK PC PRS. When we included all of the PRS in one model, all three PRS were associated with AUD criteria in COGA. Only the RISK PC and GSCAN DPW PRS were associated with AUD criteria in FT12. Overall, the unique contributions of each PRS reinforce the notion that the genetics of AUD are multifaceted, comprised of risk for level of consumption, alcohol-related problems, and behavioral disinhibition31,32. Evaluating the AUC for the combined PRS revealed the combined effect of PRSs only marginally improved the AUC, similar to recent analyses for coronary artery disease33 and ischemic stroke34. We ran a series of sensitivity analyses to test whether differences across the
