Like any genetic association study, our study has limitations that must be addressed. First, although we found a nominal association between rs4263329 and cocaine dependence, that association lost its significance after being adjusted for sex and age. Nevertheless, that is an interesting finding that warrants further studies in comparable populations. Second, our sample size, although large for this particular line of research, could be considered small for a genetic association study looking for a susceptibility gene with a small magnitude effect. Third, although the marker reported here to be associated with exclusive crack cocaine use has been correlated with functional enzymatic alterations in other studies, we did not obtain any cholinesterase measures, which would have allowed us to make a functional correlation between carrying the marker and its function in patients and controls [23], [36]. By the same token, we had no objective parameters of cocaine use in cases and controls, such as toxicological measurements of cocaine in hair or urine. The subjective ratings reported by cocaine users are known to be unreliable markers of the true amount and frequency
