Next, we performed phase 2 (replication) genotyping of the SNPs rs7849345, rs10819611 and rs1342043 which showed a trend towards significance in phase 1 genotyping using an independent replication sample, consisting of AA cocaine addicted individuals and healthy controls (samples obtained from Rutgers University Cell and DNA Repository as described in Section 2) and an independent sample of cases and controls of EA ancestry. None of these SNPs showed any statistical significance in the replication samples that survived multiple testing (Table 3A and B); however, combined analysis of the discovery and replication sample showed that rs1342043 was associated on the genotypic (p = 0.0001) as well as on the allelic level (p = 0.002), which withstood correction for multiple testing (p < 0.05) (Table 3C). The MAF of the rs1342043 C allele was higher in controls (40% vs 36%) than in cases, therefore potentially providing protection against CA in the total AA population. Sex specific combined analysis revealed an allelic association of rs7849345 in AA females (p = 0.006) whereas rs1342043 showed a significant allelic (p = 0.002) and genotypic association in AA males (p = 0.0003, data not shown).
