Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts

Am J Psychiatry. 2019 Feb 1;176(2):107-118. doi: 10.1176/appi.ajp.2018.18040369. Epub 2018 Oct 19.

Abstract

Objective: Alcohol use disorders are common conditions that have enormous social and economic consequences. Genome-wide association analyses were performed to identify genetic variants associated with a proxy measure of alcohol consumption and alcohol misuse and to explore the shared genetic basis between these measures and other substance use, psychiatric, and behavioral traits.

Method: This study used quantitative measures from the Alcohol Use Disorders Identification Test (AUDIT) from two population-based cohorts of European ancestry (UK Biobank [N=121,604] and 23andMe [N=20,328]) and performed a genome-wide association study (GWAS) meta-analysis. Two additional GWAS analyses were performed, a GWAS for AUDIT scores on items 1-3, which focus on consumption (AUDIT-C), and for scores on items 4-10, which focus on the problematic consequences of drinking (AUDIT-P).

Results: The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13; this study 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=0.76-0.92) and DSM-IV alcohol dependence (rg=0.33-0.63). AUDIT-P and AUDIT-C scores showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P score was significantly positively genetically correlated with schizophrenia (rg=0.22), major depressive disorder (rg=0.26), and attention deficit hyperactivity disorder (rg=0.23), whereas AUDIT-C score was significantly negatively genetically correlated with major depressive disorder (rg=-0.24) and ADHD (rg=-0.10). This study also used the AUDIT data in the UK Biobank to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total scores ≤4 as control subjects and those with scores ≥12 as case subjects produced a significant high genetic correlation with DSM-IV alcohol dependence (rg=0.82) while retaining most subjects.

Conclusions: AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and alcohol use disorders.

Keywords: Alcohol Abuse; Alcohol Consumption; Alcohol Dependence; Epidemiology; Genetics; Genome-Wide Association Studies.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Alcohol Dehydrogenase / genetics
  • Alcohol Drinking / genetics*
  • Alcoholism / genetics*
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Cation Transport Proteins / genetics
  • Cell Adhesion Molecules / genetics
  • Cohort Studies
  • Depressive Disorder, Major / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Klotho Proteins
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Schizophrenia / genetics
  • United Kingdom
  • Whites / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Cation Transport Proteins
  • Cell Adhesion Molecules
  • GCKR protein, human
  • JCAD protein, human
  • KLB protein, human
  • Membrane Proteins
  • SLC39A13 protein, human
  • ADH1B protein, human
  • ADH1C protein, human
  • Alcohol Dehydrogenase
  • Klotho Proteins