It is clear that our four-SNP score does not fully account for dopaminergic effects on cocaine dependence, nor are genetic influences on cocaine dependence likely to be explained by effects of the dopamine system alone. Future applications of a candidate system scoring approach may seek to include a broader selection of additional candidate systems, and may consider potential SNP-SNP interaction effects (either within genes, such as consideration of haplotype blocks, or between SNPs located in separate genes), although these would necessarily increase the complexity of the model. Of course, even the inclusion of genes from numerous systems a priori hypothesized to be involved in the target phenotype will not allow for this candidate system scoring approach to identify new variants or systems of interest, a goal for which the GWAS and genome-wide scoring approaches are clearly well-suited, given adequate sample sizes.
