Because SAGE is composed of individuals from three independent studies, each ascertained for a different substance dependence, we performed stratified analyses both by study and by nicotine dependence and alcohol dependence to determine if there existed a subset of subjects in which the association was most pronounced. The top SNP associated with DSM-5 cocaine use disorder (rs9298626) in the whole SAGE dataset was significantly associated with DSM5 cocaine use disorder in the COGA subset and showed a trend in the same direction in the FSCD and COGEND subsets. Furthermore, when individuals from the whole dataset were stratified by DSM-5 alcohol use disorder, or FTND nicotine dependence there was evidence of association between rs9298626 and cocaine use disorder in both groups (Table 3). This suggests that the observed associations are not an artifact of ascertainment. This analysis suggests that this SNP is associated with DSM-5 cocaine use disorder and that the CHRNB3-A6 locus is robustly associated with DSM-5 cocaine use disorder, regardless of comorbidity or ascertainment.
