Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)
Year: 2018
Type: preprint
Study design: Observational Study
Abstract: 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 (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 (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.
DOI: 10.1101/275917
Authors: Sandra Sanchez-Roige, Abraham A. Palmer, Pierre Fontanillas, Sarah L. Elson, Mark J. Adams, David M. Howard, Howard J. Edenberg, Gail Davies, Richard C. Crist, Ian J. Deary, Andrew M. McIntosh, Toni-Kim Clarke
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2794263701