TY - JOUR T1 - Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,958) JF - bioRxiv DO - 10.1101/275917 SP - 275917 AU - Sandra Sanchez-Roige AU - Abraham A. Palmer AU - Pierre Fontanillas AU - Sarah L. Elson AU - The 23andMe Research Team AU - Substance Use Disorder Working Group of the Psychiatric Genomics Consortium AU - Mark J. Adams AU - David M. Howard AU - Howard J. Edenberg AU - Gail Davies AU - Richard C. Crist AU - Ian J. Deary AU - Andrew M. McIntosh AU - Toni-Kim Clarke Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/03/08/275917.abstract N2 - 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=121,630) 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 11 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 (rg=0.78-0.96) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) alcohol dependence (rg=0.33-0.64). 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 (rg=0.22, p=1.2×10−10), major depressive disorder (rg=0.26, p=4.5×10−5), and ADHD (rg=0.23, p=1.2×10−5), whereas AUDIT-C was negatively genetically correlated with major depressive disorder (rg=-0.23, p=3.2×10−3) and ADHD (rg=-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 (rg=0.82, p=3.9×10−6) 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. ER -