We have presented the largest GWAS meta-analysis of AUDIT total score to date, using large population-based cohorts from UKB and 23andMe. We identified novel associations with AUDIT total score; the genes located in these regions include JCAD and SLC39A8. We found evidence for association in several loci previously associated with alcohol use via single-variant and gene-based analyses (i.e. KLB, GCKR, CADM2). The SNP heritability of all AUDIT phenotypes ranged from 9–12% demonstrating that common genetic factors account for a prominent proportion of the variation in alcohol use phenotypes. Furthermore, we showed that there is shared genetic architecture between AUDIT scores and other alcohol and substance use phenotypes. AUDIT-P showed a positive genetic correlation with several psychiatric diseases, distinguishing AUDIT-P from AUDIT-C. Finally, using LDSC, we identified thresholds for dichotomizing AUDIT total score (AUDIT score ≥12 to define cases, and ≤4 to define controls) that maximize the genetic correlation with alcohol dependence while retaining a large number of participants.
