Genome-wide association study meta-analysis of the alcohol use disorders identification test (AUDIT) in two population-based cohorts
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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.
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Similar linkages have been found in the FGF21 co-receptor Klb, primarily focused on alcohol intake.
“Similar linkages have also been found in the FGF21 co-receptor Klb, although these associations have primarily focused on alcohol intake”
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- Authors
- Sanchez-Roige, S., Palmer, A. A., Fontanillas, P., Elson, S. L., the 23andMe Research Team, T. S. U. D. W. G. O. T. P. G. C., Adams, M. J., Howard, D. M., Edenberg, H. J., Davies, G., Crist, R. C., Deary, I. J., McIntosh, A. M., & Clarke, T.-K.
- Affiliations
- From the Department of Psychiatry and the Institute for Genomic Medicine, University of California San Diego, La Jolla; 23andMe, Inc., Mountain View, Calif.; the Division of Psychiatry, the Department of Psychology, and the Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, U.K.; the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis; and the Translational Research Laboratories, Center for Neurobiology and...
- University of California San Diego (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2019-02-01
- Volume
- 176
- Issue
- 2
- Pages
- 107-118
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC6365681
- OpenAlex
- W2950625872
- Cited by
- 430
- References
- 46
- Citations by year
- 2026: 28 · 2025: 51 · 2024: 54 · 2023: 62 · 2022: 63 · 2021: 52 · 2020: 75 · 2019: 40 · 2018: 5
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- Wellcome Trust (104036/Z/14/Z, 104036)
- Centre for Cognitive Ageing and Cognitive Epidemiology (MR/K026992/1)
- Directorate for Biological Sciences
- Medical Research Council (MR/K026992/1, 104036/Z/14/Z, MC_PC_17228)
- Biotechnology and Biological Sciences Research Council
- National Institute of Mental Health (U01MH109536, R25MH081482)
- National Institute on Drug Abuse (P50DA037844)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- alcoholism, auditing, alcohol consumption, alcohol abuse, genetic susceptibility loci, genetic correlation, AUDIT-C, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder, ADH1B, ADH1C, KLB, GCKR, mental illness
- MeSH terms
- Klotho Proteins, Alcohol Dehydrogenase, Alcohol Drinking, Alcoholism, Attention Deficit Disorder with Hyperactivity, Major Depressive Disorder, Female, United Kingdom, Humans, Male, Membrane Proteins, Middle Aged, Schizophrenia, Cohort Studies, Cell Adhesion Molecules, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Cation Transport Proteins, White People, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study
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