It is estimated that approximately 2.1% of US residents have used cocaine in the past month, the second most prevalent nonmedical drug to marijuana.49 Similar to nicotine and alcohol dependence, cocaine dependence has a strong component of heritability: siblings of cocaine-dependent probands had an estimated relative risk of 1.8 of developing cocaine dependence compared with probands without cocaine-dependent siblings.50 Because of the hypothesis that common genetic factors may lead to dependence on various classes of drugs, a study evaluated the relationship between cocaine dependence and rs16969968, the nonsynonymous CHRNA5 SNP associated with increased risk for nicotine dependence.51 The minor allele of rs16969968 that is associated with increased risk for nicotine dependence is associated with decreased risk for cocaine dependence. The bidirectional association is hypothesized to be due to the involvement of nAChRs with excitatory and inhibitory modulation of dopamine-mediated reward pathways. A negative association was also seen between the CHRNA5 SNP rs588765 and alcohol dependence in a sample that was heavily comorbid with cocaine dependence.52 This association suggests that the CHRNA5 gene may play a dual role in modulating susceptibility to addiction via the different mechanisms of action of cocaine and nicotine.
