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.