We have reported the largest GWAS of AUDIT ever undertaken. We replicated previously identified signals (i.e. ADH1B, ADH1C; KLB; GCKR), and identified novel GWAS signal (i.e. JACD, SLC39A8) associated with AUDIT. We show that different portions of the AUDIT (AUDIT-C, AUDIT-P) correlate with distinct traits, which will aid in dissecting genetic vulnerability towards alcohol use and dependence. The genetic factors that predispose to high alcohol consumption inevitably overlap with those for problem drinking, as heavy drinking is generally a prerequisite for the development of hazardous use and dependence. However, not everyone who consumes alcohol experiences the same level of harmful consequences. By studying the different subsets of AUDIT, we identify genetic factors that may be specific to problem drinking. Larger studies of cohorts with a wider range of AUDIT-P scores are required to both replicate and expand these findings. Finally, we describe an alternative strategy to rigorous ascertainment for genetic studies of AUD, i.e. AUDIT score ≥12 to define cases and ≤4 to define controls, which could be used to achieve large sample sizes in a cost-efficient manner.
