The D398N amino acid change at rs16969968 demonstrates large differences in allele frequency across populations. The minor allele frequency (MAF) is 33% in our EA sample and only 5% in our AA sample. In the HapMap Yoruba sample, rs16969968 is monomorphic, so our African American sample likely demonstrates population admixture. Though homogeneous samples have been promoted as a resource to increase power to detect association, it is with outbred and admixed samples and two different populations (European-American and African-American) that we have narrowed an association signal to a likely functional variant involved in substance dependence. These results underscore the importance of expanding current genetic disease mapping studies to include diverse population samples beyond those of European descent.
