In this Article, to improve our understanding of the biology of PAU in multiple populations, we conducted substantially larger ancestry-specific GWAS of PAU followed by a cross-ancestry meta-analysis in 1,079,947 individuals from multiple cohorts. We identified 85 independent risk variants in participants of EUR ancestry and 110 in the within-ancestry and cross-ancestry meta-analyses. We investigated the shared genetic architectures of PAU across different ancestries and performed fine mapping for causal variants by combining information from multiple ancestries. We identified dozens of genes linked to brain with convergent evidence. A drug repurposing analysis identified potential medications that have the potential to inform further pharmacological studies. Overall, these findings substantially augment the number of loci that contribute to the risk of PAU, which increases our power to investigate the causal relationships of PAU with other diseases, demonstrating similarity in the genetic architecture across ancestries and helps identify potential druggable targets whose therapeutic potential requires empirical evaluation.
