In the present study, we employed a cluster analytic approach to derive subtypes of cocaine use and related behaviors that were more homogeneous than the group defined by DSM diagnosis in terms of their clinical features, including frequency and intensity of cocaine use, cocaine withdrawal symptoms, cocaine-related adverse effects and treatment history. We hypothesized that the subtypes would be superior to DSM-IV CD as traits for variant detection. Our association analysis provided support for the hypothesis. The association results with the two derived subtypes showed more significant P values for six of eight SNPs in the analysis of main effects (Table V) and seven of eight SNP pairs of epistatic effects (Table VI). Moreover, one variant, rs11939815 in CLOCK, was significantly associated only with Group 4 in AAs. An advantage of the subtyping approach to trait definition was also evident in the pair-wise epistatic effect tests, in which the most significant results were for variants associated with either of the two derived subtypes for all SNP pairs except rs4591574 and rs8041610.
