We report here the largest multi-ancestry GWAS for PAU so far, comprising over 1 million individuals and including 165,952 AUD/AD cases. The inclusion of multiple ancestries both broadened the findings and demonstrated that the genetic architecture of PAU is substantially shared across these populations. Cross-ancestry fine mapping improved the identification of potential causal variants, and cross-ancestry PRS analysis was a better predictor of alcohol-related traits in an independent sample than single-ancestry PRS. We prioritized multiple genes with convergent evidence linking association to PAU with gene expression and chromatin interaction in the brain, and we investigated genetic correlations with multiple traits in AFR, also not possible previously. On the basis of these advances, we identified existing medications predicted to be potential treatments for PAU, which can be tested.
