A third notable observation is that the alcohol consumption PRS explained the most variance for alcohol use (R2 ≤ 1.39%), which represents drinking at least once a month for six consecutive months at some point during the lifetime and is ubiquitously endorsed in this sample (89.9%); this is likely also common in the UK Biobank sample. In fact, the addition of the PRS significantly improved the AUC for alcohol use, compared to a model of covariates only. It is likely that alcohol consumption in the UK Biobank represents normative patterns of drinking and does not sufficiently index problem drinking. Thus, in COGA, PRS derived from such an index of normative alcohol consumption was most closely related to an equally heterogeneous measure of drinking that included normative (and problem) drinkers. We were unable to examine typical alcohol consumption as it was not assessed in COGA in a similar manner as UK Biobank. Nonetheless, our results suggest that in this high-risk sample, PRS from large-scale GWAS of alcohol consumption were more strongly associated with propensity to alcohol use than with measures of problem drinking or disorder.
