Finally, our comprehensive PheWAS analyses have linked different facets of AUD liability (via the latent factor-based Consumption and Problems PRSs) to a myriad of health-related outcomes in a large, independent biobank. We found that the Consumption PRS was consistently negatively associated with a broad range of metabolic and congenital conditions. While it is possible that there is still residual bias in the discovery GWAS, it is important to note that this pattern of paradoxical associations with Consumption is not observed in the genetic correlation analyses. Thus, it is possible that these negative associations are illustrative of selection bias or other confounding in BioVU (43), where patients with certain conditions may elect to not drink due to unmeasured factors (e.g., family history, medical advice, contraindications for prescriptions). Mirroring the genetic correlation results, we also found that the Problems PRS was uniquely associated with numerous psychiatric disorders that are commonly reported to co-occur with AUD. However, and importantly, we identified that the associations between Problems PRS and mental health did not persist in the absence of the clinical manifestation of AUD. These
