Family-based study of DRD2 alleles in alcohol and drug dependence

Numerous case-control studies have addressed the hypothesis that variant al leles of the dopamine D2 receptor gene (DRD2) increase the liability for al cohol and/or drug dependence, and both positive and negative results have b een reported, Because population frequencies of these alleles vary consider ably, the conflicting results could be due to population stratification bia s, Using the transmission disequilibrium test, the present study examined l inkage disequilibrium of alcohol and drug (opioid and/or cocaine) dependenc e with three DRD2 polymorphic systems: (a) TaqI A, (b) TaqI D, and (c) the functional -141CIns/Del promoter systems. DNA samples were collected from s mall nuclear families (SNFs), where one or more offspring met DSM-III-R or DSM-IV criteria for alcohol and/or drug dependence. Because positive associ ation between DRD2 alleles and alcohol and/or drug dependence has been repo rted only in populations of European ancestry, we limited the present study to European Americans (EAs), No evidence for linkage disequilibrium was fo und for any of the polymorphic systems when examined in relation to any sub stance dependence, alcohol dependence (with or without drug dependence), or drug dependence (with or without alcohol dependence). These results are co nsistent with those from a recent family-based study of alcohol dependence, Together, these studies suggest that the conflicting findings from case-co ntrol studies of the association between alleles of DRD2 and substance depe ndence may be attributable to population stratification in some samples, Am . J. Med. Genet. (Neuropsychiatr. Genet.) 96:659-664 2000, (C) 2000 Wiley-L iss, Inc.