We performed two independent PheWASs of Consumption and Problems PRSs to identify whether these two factors would show different patterns of genetic associations with medical outcomes. Of 1,335 phenotypes, 15 were FDR-significantly associated with Consumption (Figure 5, Table S36) and 17 with Problems (Table S37). Both factors were significantly associated with AUD and other tobacco and substance use disorders. Replicating our previous results for AUDIT-C and AUDIT-P, we observed paradoxical negative associations between Consumption and metabolic conditions, including diabetes mellitus and obesity phenotypes, whereas Problems was primarily positively associated with other psychiatric disorders, including depression, anxiety disorder, bipolar disorder, schizophrenia and suicidal ideation or attempt. Intriguingly, Problems was also negatively associated with type 2 diabetes with renal manifestations. Most of the associations did not persist after correcting for AUD, although the direction of effects remained consistent (Tables S38–39).
