In this study we investigated whether polymorphisms in the NCS-1 gene confer risk to CA using a discovery a sample of AA subjects and replication samples of individuals of both AA and EA ancestry. While we found a strong association of rs1342043 with CA in AA individuals in the discovery sample, our replication attempt failed to demonstrate a statistically significant association; however, combining AA discovery and replication sample showed a statistically significant effect (Table 3C). Furthermore, our results provide evidence for a gender-specific association between NCS-1 polymorphisms and CA. The variant rs1342043 was associated with cocaine dependence in AA males (genotypic p = 0.005), while the rs7849345 was associated significantly with CA in AA females (genotypic p = 0.005, allelic p = 0.0016), suggesting a differential influence of these SNPs in males and females. The C allele in rs1342043 in the total population as well as in males and the T allele of rs7849345 in females demonstrated a protective effect against cocaine addiction in the AA populations. No significant associations were observed in EA population.
