The current study sought to identify SNP variation that was associated with individual differences in cocaine dependence symptoms. It was hypothesized that in studies with modest sample sizes, or small effect sizes, these effects could be most reliably detected and replicated in the aggregate. Given that there is strong evidence implicating the dopamine system in cocaine dependence, we sought to improve our power to detect what were expected to be small effects of individual SNPs on cocaine dependence by limiting our analyses to SNPs in a selected, core set of autosomal genes that are definitely and directly involved in the dopamine system and by examining the joint effect of these SNPs. We therefore constructed a genetic risk score from a subset of a genome-wide data set, including only SNPs from selected dopaminergic genes. The specific SNPs most strongly associated with cocaine dependence symptoms were first identified in an initial discovery sample. The replication of these top SNPs’ aggregate effect on cocaine dependence was then examined in an independent testing sample. Because substantial heritable variance is common across multiple substances of
