In this study, we performed a GWAS meta-analysis using the UK Biobank (UKB; N = 121,604) and the previously published 23andMe cohort (N = 20,328)(10), yielding the largest GWAS meta-analysis of AUDIT total score to date (N = 141,932). Using only the UKB cohort, we also sought to determine whether the alcohol consumption component of the AUDIT had a genetic architecture distinct from the dependence and harmful use components by performing GWASs of consumption “AUDIT-C” (items 1–3) and problems “AUDIT-P” (items 4–10). Linkage Disequilibrium Score regression (LDSC)(16) was used to calculate genetic correlations between AUDIT measures and other substance use, psychiatric, and behavioral traits. We also calculated genetic correlations with obesity and blood lipid traits, as these have previously been shown to associate with alcohol consumption (9, 10). We hypothesized that AUDIT-P would correlate more strongly with measures of hazardous substance use, including alcohol dependence, and other psychiatric conditions. Finally, in order to determine the thresholds for dichotomizing AUDIT total score that would most closely approximate alcohol dependence, we converted continuous AUDIT total score into cases and controls using different thresholds, performed GWAS on each, and calculated the genetic correlation with DSM-IV alcohol dependence (13).
