Second, and perhaps most importantly, we found that Consumption was a good genetic proxy of AUD when appropriate weights were applied to the individual items using Genomic Structural Equation Modeling. This is a striking change from previous investigations into the divergent genetic bases of alcohol consumption and problematic use, including our own prior analyses of AUDIT. GWASs of alcohol consumption phenotypes have consistently reported low-to-moderate overlap with AUDs that have surprised many researchers (2–5), and even paradoxical negative associations with a variety of diseases and disorders. Our multivariate approach has ameliorated these issues, producing an aggregate measure of alcohol consumption that is more consistent with the known patterns of alcohol phenotype associations established in the existing body of literature, such as a strong genetic correlation with alcohol dependence. Furthermore, we used genetic correlation analyses to characterize the residual genetic variance in frequency of consumption (Frequency Residual) that is unrelated to other AUDIT items. These analyses revealed that Frequency Residual had consistently positive associations with measures of socioeconomic status and consistently negative associations with measures of substance use and psychopathology. Indeed,
