Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts

Alcohol use disorders ( AUD ) are common conditions that have enormous social and economic consequences. We obtained quantitative measures using the Alcohol Use Disorder Identification Test ( AUDIT ) from two population-based cohorts of European ancestry: UK Biobank ( UKB ; N=121,604) and 23andMe (N=20,328) and performed a genome-wide association study (GWAS) meta-analysis. We also performed GWAS for AUDIT items 1–3, which focus on consumption ( AUDIT-C ), and for items 4–10, which focus on the problematic consequences of drinking ( AUDIT-P ). The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13 ; we also replicated previously identified signals in the genes ADH1B, ADH1C , KLB , and GCKR . The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (r g =0.76–0.92) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) alcohol dependence (r g =0.33–0.63). AUDIT-P and AUDIT-C showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P was positively genetically correlated with schizophrenia (r g =0.22, p=3.0×10−10), major depressive disorder (r g =0.26, p=5.6×10−3), and attention-deficit/hyperactivity disorder (ADHD; r g =0.23, p=1.1×10−5), whereas AUDIT-C was negatively genetically correlated with major depressive disorder (r g =−0.24, p=3.7×10−3) and ADHD (r g =−0.10, p=1.8×10−2). We also used the AUDIT data in the UKB to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total score of ≤4 as controls and ≥12 as cases produced a high genetic correlation with DSM-IV alcohol dependence (r g =0.82, p=3.2×10−6) while retaining most subjects. We conclude that AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and AUD.