Given our modest sample size, and substantial evidence implicating the dopamine system in cocaine dependence, we sought to improve our power to detect SNP effects on cocaine dependence by limiting our analyses to SNPs located within a small set of dopamine-related genes and by examining the effects of these SNPs in aggregate. Although such a specific (e.g. candidate system) approach limits the potential for novel findings, such a limitation in scope is informed by the theoretical effect size of the influence of individual SNPs on complex phenotypes, such as substance dependence. The identification of four SNPs explaining 0.55% of the testing sample variance may appear both limited in scope and effect size, but this puts the individual SNPs at effect sizes of just over 0.1% each, which is well-aligned with current expectations for effect sizes of common variants.
