Which alcohol use disorder criteria contribute to the association of ADH1B with alcohol dependence?: ADH1B variants and AUD
Open accessAbstract
Although alcohol dependence (AD) is approximately 50% heritable, little is known about how specific genetic loci affect AD risk. In a genome-wide association study (GWAS), we identified highly significant associations between two population-specific functional variants in the alcohol dehydrogenase 1B gene (ADH1B) and AD in African-Americans (AAs; rs2066702) and European-Americans (EAs; rs1229984). In the current study, we determined which specific diagnostic criteria contributed to the observed associations of ADH1B SNPs with AD. Our analysis included both the DSM-IV and DSM-5 diagnostic systems. We also investigated the relationship of ADH1B variants to the maximum number of drinks consumed in a 24-hour period (MaxDrinks), a presumed intermediate phenotype of AD. We found that, although all criteria made strong individual contributions to the associations, the largest contributions came from those reflecting neuroadaptation: tolerance (rs2066702) and withdrawal (rs1229984). Overall, evidence for association with DSM-5 criteria was slightly stronger than for DSM-IV criteria. For rs2066702, results were similar for DSM-IV and DSM-5 criteria. However, the most significant DSM-5 criterion associated with rs1229984 was alcohol-related social/interpersonal problems. Both ADH1B variants were associated with MaxDrinks, a measure of innate tolerance, and MaxDrinks mediated the associations between ADH1B and alcohol outcomes. We replicated the findings for rs2066702 and tolerance in an independent sample of AAs. Taken together, these results suggest that variation in ADH1B affects the adaptation to heavy drinking, highlighting population-specific differences in genetic risk for AUD. They also suggest that the revisions reflected in DSM-5 AUD may enhance the utility of that diagnosis for gene finding.
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ADH1B genotypes (alcohol), while associated with DSM criteria, are not integrated within the DSM framework.
“For addictive disorders, the story is much the same and, for example, ADH1B genotypes (alcohol), while associated with DSM criteria, are not integrated within this framework [11].”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [11]
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- Authors
- Hart, A. B., Lynch, K. G., Farrer, L., Gelernter, J., & Kranzler, H. R.
- Affiliations
- University of Pennsylvania (US)
- Boston University (US)
- Yale University (US)
- Philadelphia VA Medical Center (US)
- Corresponding author
- Kranzler, Henry R.
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2015-04-01
- Volume
- 21
- Issue
- 4
- Pages
- 924-938
- ISSN
- 1355-6215 (ISSN-L)
- PMC
- PMC4591076
- OpenAlex
- W1549899031
- Cited by
- 17
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, T32 DA028874)
- VA Connecticut
- Philadelphia VA MIRECCs
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- alcoholism, ADH1B, alcohol dehydrogenase, alcohol tolerance, alcohol withdrawal, DSM-5 diagnostic criteria, DSM-IV diagnostic criteria, alcohol-related social problems, genetic risk, African Americans, European Americans, single nucleotide polymorphisms
- MeSH terms
- Adult, Alcohol Dehydrogenase, Alcoholism, Black or African American, Drinking Behavior, Female, Humans, Male, Alcohol-Related Disorders, White People, Genome-Wide Association Study
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