In the current analysis, we tested PRS in two target samples, a population-based sample and a clinically ascertained sample of families deeply affected by AUD, to evaluate the current state of alcohol-related PRS in relation to AUD and identifying those at heightened risk. We use several discovery samples from large-scale GWAS to create three PRS: a meta-analysis of two GWASs on alcohol-related problems5,6, a recent large-scale GWAS of alcohol consumption8, and a GWAS for risky behaviors, including alcohol use13. We chose to test PRS based on multiple alcohol-related GWAS because multiple lines of evidence indicate alcohol consumption and dependence have only partially shared genetic etiology5,6,14,15. Additionally, we include a PRS for general risk behavior as there is robust evidence that the genetic risk for alcohol and other substance use disorders is shared with other disorders and behaviors related to reduced inhibitory control16–18. Similar to recent work for specific medical conditions11, we compare the upper end of the PRS distribution at various thresholds (top 20, 10, and 5%) to examine whether focusing on these upper parts of the distribution provide additional
