ArticleBehavioral and brain functions : BBF2008
Recessive genetic mode of an ADH4 variant in substance dependence in African-Americans: A model of utility of the HWD test.
Article in Behavioral and brain functions : BBF, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians.Human genetics · 2012Pooled it
- Identification of prognostic biomarkers for patients with hepatocellular carcinoma after hepatectomy.Oncology reports · 2019Article
- Sex difference of autosomal alleles in populations of European and African descent.Genes & genomics · 2015Article
- Exploring the genetic architecture of alcohol dependence in African-Americans via analysis of a genomewide set of common variants.Human genetics · 2014Article
- Less drinking, yet more problems: understanding African American drinking and related problems.Psychological bulletin · 2014Review
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundIn our previous studies, we reported positive associations between seven ADH4 polymorphisms and substance dependence [i.e., alcohol dependence (AD) and/or drug dependence (DD)] in European-Americans (EAs). In the present study, we address the relationship between ADH4 variation and substance dependence in an African-American (AA) population, and report evidence that supports an association between a different ADH4 polymorphism (rs2226896) and these phenotypes in AAs.
methodsTwo family-based association study methods, i.e., TDT and FBAT, were applied to test the relationship between ADH4 variation and substance dependence in Sample 3 (112 small nuclear families) and in Sample 4 (632 pedigrees), respectively. A population-based case-control association study method was also applied to test this relationship in 1303 unrelated subjects, with and without controlling for admixture effects. Finally, a Hardy-Weinberg Disequilibrium (HWD) test was applied to examine the association in the case-only sample, infer the genetic disease models, and distinguish the disease and non-disease factors contributing to HWD.
resultsThe marker examined was found to be in significant HWD in AA alcoholics (p = 0.0071) and drug dependent subjects (p = 0.0341), but in Hardy-Weinberg Equilibrium (HWE) in all other subgroups. Other association methods failed to detect any association between this variation and phenotypes. The best-fit genetic disease model for this marker is a recessive genetic model.
conclusionADH4 variation might play a role in risk for substance dependence in AAs, potentially via a recessive mechanism. Under certain conditions, the HWD test could be a more powerful association method than conventional family-based and population-based case-control association analyses, for which, the present study provides an extreme example.
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