This cross-population contrast method, applied to European-American and African-American case-control samples, was successful in refining an association signal between SNPs in the CHRNA5-CHRNA3-CHRNB4 gene cluster and cocaine dependence, with the results highlighting a group of SNPs that includes rs16969968, a non-synonymous coding SNP in CHRNA5. Among the 10 genotyped SNPs, which are highly correlated in populations of European descent, three are filtered out due to significant evidence for heterogeneity of association in the two population samples, two others have p-values of 0.06, and the remaining SNPs include rs16969968, which had heterogeneity p-value 0.75 and similar odds ratios in EAs and AAs. This result further highlights this variant as a potential causative variant, as it adds a new line of evidence – no significant heterogeneity between populations for rs16969968 – to existing knowledge that this SNP causes an amino acid change and is conserved across species. This interpretation must be tempered by the fact that the power to rule out this SNP is reduced due to the considerable allele frequency difference in the EA versus AA samples. With a larger sample
