Lohoff et al. (2008) reported an allelic and haplotypic association between COMT and cocaine dependence in individuals of African descent. The aim of our study was to examine potential functional variation at the COMT locus in CIP in both European-Americans (EAs) and African-Americans (AAs) by using SNP-haplotype analysis and identifying possible signatures of positive natural selection. These families were recruited for genetic linkage studies of cocaine or opioid dependence (Gelernter et al, 2005; Gelernter et al, 2006). (The first of these studies also identified a significant genetic linkage of CIP to markers on chromosome 9.) On the basis of COMT single SNP analysis, we found several nominally-significant associations. In addition, the rs737866-rs4680-rs174696 haplotype showed significant association in EA families and in both EA and AA unrelated populations. Haplotype A-A-T was associated with CIP in EA families and in unrelated AAs. The A-G-T haplotype frequency differed significantly only in male EA unrelateds based on the presence of CIP.
