Our study has several limitations. First, although all of the most significant variants are supported by surrounding SNPs, SNPs located at the association peak for several of the top loci are located in intergenic regions for which there is little evidence of a functional impact. Second, a high proportion of stimulant-dependent cases in the discovery and replication cohorts are dependent on other substances, so our results might not generalize to all individuals with amphetamine-related stimulant dependence. Third, the inclusion of both exposed and unexposed controls in this study may have reduced power due to misclassification; i.e. come controls might carry significant risk for stimulant dependence but were not exposed. Fourth, the number of stimulant-dependent cases is small for a GWAS and, not surprisingly, several associated variants have a large effect size. This is particularly true of the AA sample. Fifth, it is possible that some of our results were diluted because the interview instrument does not distinguish the use of methamphetamine from several other stimulant drugs. Finally, the significant enrichment for nicotinic acetylcholine receptor genes in the pathway analysis may
