The current study sought to demonstrate a method of candidate system scoring in a sample that would be underpowered for genome-wide analytic approaches. To that end, we aimed to identify dopaminergic SNP variation that was associated with individual differences in cocaine dependence symptoms. Given the strong evidence implicating the dopamine system in cocaine dependence, we attempted to improve our power to detect what were expected to be small effects of individual SNPs on cocaine dependence symptoms 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 effect of these SNPs in the aggregate. We found evidence for an association between cocaine dependence symptoms and dopamine-related candidate genes at the biological system level. The optimal risk score, utilizing regression weights derived in the training sample by independently testing each SNP’s association with cocaine dependence symptoms, incorporated four SNPs (one each from four separate genes: DBH, DRD1, DRD3, and DRD4) and explained 0.55% of the sample variance in the “testing” sample (p = 0.037).
