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 information in identifying those at increased risk of developing an AUD. We acknowledge the exploratory nature of these analyses and the arbitrary nature of our thresholds in the absence of well-defined clinical risk scores, such as those for medical conditions like hypertension. Finally, we test the association of these PRSs with other substance use disorders (including nicotine and illicit substance use disorders), based on the robust finding that substance use disorders share an underlying genetic architecture, with the majority of the heritability shared across substances16–18.
