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Related Experiment Video

Updated: May 18, 2026

Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
05:12

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Published on: June 23, 2023

Rare ADH variant constellations are specific for alcohol dependence.

Lingjun Zuo1, Heping Zhang, Robert T Malison

  • 1Department of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA.

Alcohol and Alcoholism (Oxford, Oxfordshire)
|September 29, 2012
PubMed
Summary

Rare alcohol dehydrogenase (ADH) gene variants are specifically linked to alcohol dependence. These findings suggest the ADH gene cluster may contain causal variants for this disorder.

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Area of Science:

  • Genetics
  • Neuroscience
  • Pharmacogenomics

Background:

  • Functional alcohol dehydrogenase (ADH) gene variants, such as ADH1B*2, ADH1B*3, and ADH1C*2, are known to influence alcohol dependence risk.
  • These impactful variants are typically rare in most populations, necessitating focused investigation.

Purpose of the Study:

  • To comprehensively examine the association between rare ADH gene variants (minor allele frequency <0.05) and alcohol dependence.
  • To investigate these associations in the context of other neuropsychiatric and neurological disorders as a reference.

Main Methods:

  • Analysis of 49,358 subjects across 22 independent cohorts, including 3 cohorts with alcohol dependence.
  • Imputation of the entire ADH gene cluster (Chr4) using whole-genome sequencing reference panels.
  • Stringent cleaning of phenotype and genotype data, focusing on 870 single nucleotide polymorphisms with 0 < MAF < 0.05 for association analysis.

Main Results:

  • A significant association was found between rare ADH gene variants and alcohol dependence in European-Americans, European-Australians, and African-Americans.
  • Association signals primarily originated from ADH6, ADH7, ADH1B, and ADH1C, with a notable replicable association from a rare ADH6 variant constellation.
  • No significant associations were observed between these rare ADH variants and other neuropsychiatric diseases examined.

Conclusions:

  • Rare ADH gene variants demonstrate specificity for alcohol dependence.
  • The ADH gene cluster is a potential source of causal variants for alcohol dependence.