We also found that PAU was significantly genetically correlated with 138 other traits. The top correlations were with substance use and substance-related disorders, MDD, schizophrenia, and several other neuropsychiatric traits. In a conceptually similar analysis, we performed a PheWAS of PAU PRS in BioVU, which confirmed in an independent sample the genetic correlations between PAU and multiple substance use disorders, mood disorders, and other psychiatric traits. We also used MR to infer causal effects of the above traits on liability to AUD (we tested AUD excluding UKB samples to avoid sample overlap) using selected genetic instruments. We found evidence of positive causal relationships from DrnkWk (bi-directional), ever smoked regularly, worry sub-cluster, and number of sexual partners, while cognitive performance and educational attainment (bi-directional) showed protective effects on liability to AUD. In comparison, we detected few causal effects from AUD to other traits, possibly because of lack of power since there are fewer instrumental variants for AUD available in our study than for many comparison GWAS.
