Initially, the standardized residuals of cocaine dependence symptom counts were regressed separately on each SNP within the training sample. SNPs were coded as 0/1/2 to indicate the number of minor (i.e., less frequent) alleles present for a given individual. This coding scheme assumes a priori that allelic effects will be additive in nature. Although this may decrease our ability to detect alleles with dominant effects that are only weakly tagged by our genotyped SNPs (Vukcevic et al. 2011), additive allelic effects likely account for the majority of genetic variance within a complex phenotype such as cocaine dependence (Hill et al. 2008). It has been suggested that interactions among SNPs could also account for substantial heritable variance. However, such epistatic models may often be statistically indistinguishable from models in which genetic effects are assumed to be primarily additive, and substantially greater sample sizes are required to achieve adequate power to estimate interactive effects among SNPs, over and above any main effects of those same SNPs (Zuk et al., in press). Given the additional multiple testing burden of testing more than one effect model for each SNP, we chose to assume an additive model for all tests.
