reversal of the odds ratio for rs16969968, which is protective for cocaine dependence but a risk factor for nicotine dependence, as well as our observation that in the CHRNB3-A6 locus on chromosome 8, there are variants associated with protection against nicotine dependence, in addition to variants associated with risk for DSM-5 cocaine use disorder and bipolar disorder. Since the finding in CHRNA5 on chromosome 15 is the only association with cocaine dependence to be successfully replicated, it would be interesting to examine the CHRNB3-A6 region in other datasets that have assessed cocaine dependence phenotypes, as well as to analyze datasets of other ethnicities. Currently, there is no evidence that either of the variants reported here are correlated with SNPs that have known functional consequences. However, rs4952 and rs4953 are both synonymous variants in CHRNB3 and may therefore have some, as yet unknown effect on transcription or translation of CHRNB3 mRNA. Overall, our findings underscore the comorbidity among drug dependencies and corroborate the role of nicotinic receptors in cocaine-related phenotypes. This study represents one of only a few to implicate specific variants in cocaine dependence phenotypes and the first to implicate low frequency variants within the CHRNB3-A6 locus in risk for
