[2–5]. PAU captures pathological alcohol use: physiological dependence and/or significant psychological, social or medical consequences. Quantity/frequency measures may capture alcohol use that is in the normal, or anyway nonpathological, range. As such, we argue that although quantity/frequency measures are important for understanding the biology of habitual alcohol use, PAU is the more clinically important trait. Thus, we did not meta-analyze PAU with DrnkWk directly, but used MTAG analysis instead, recognizing that they are different traits. These circumstances underscore the need to assemble a large GWAS sample of PAU to inform its biology, and our study moves towards this goal via the identification of numerous previously-unidentified risk loci – we increased known PAU loci from 10 to 29, nearly tripling our knowledge of specific risk regions. Similarly, we identified 66 gene-based associations, of which 46 were novel – again roughly tripling current knowledge. MTAG analysis increased locus discovery to 119, representing 76 independent loci, by leveraging information from DrnkWk [9]. By the same token, we provide a major increment in information about the biology of PAU, providing considerable fodder for future studies that will be required to delineate the biology and function associated with each risk variant. We anticipate that knowledge
