Recessive genetic mode of an ADH4 variant in substance dependence in African-Americans: A model of utility of the HWD test
Open Access
- 18 September 2008
- journal article
- research article
- Published by Springer Nature in Behavioral and Brain Functions
- Vol. 4 (1) , 42
- https://doi.org/10.1186/1744-9081-4-42
Abstract
Background: In our previous studies, we reported positive associations between sevenADH4polymorphisms 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 betweenADH4variation and substance dependence in an African-American (AA) population, and report evidence that supports an association between a differentADH4polymorphism (rs2226896) and these phenotypes in AAs.Methods: Two family-based association study methods, i.e., TDT and FBAT, were applied to test the relationship betweenADH4variation 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.Results: The 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.Conclusion: ADH4variation 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.This publication has 57 references indexed in Scilit:
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