We tested the bi-directional causal effects between other traits and AUD (MVP+PGC), rather than PAU; the UKB AUDIT-P GWAS sample was excluded to minimize overlap with other GWAS for putative exposures. (When we refer to exposure having causal effect on outcome, this should be understood to mean susceptibility or liability to exposure having causal effect on susceptibility or liability to outcome.) We limited the exposures to those genetically correlated with PAU, and which yielded >10 available instruments to have a robust causal estimate. Among the 15 tested exposures on AUD, seven showed evidence of a causal effect on liability to AUD (Table 2). DrnkWk and ever smoked regularly have a positive causal effect on AUD risk by all four methods, without violating MR assumptions through horizontal pleiotropy (MR-Egger intercept p > 0.05). General risk tolerance was causally related to AUD risk, and the estimate was robust after correction for horizontal pleiotropy. The “worry” sub-cluster of neuroticism and number of sexual partners show evidence of positive causal effects on liability to AUD with at least one method, while cognitive performance and
