Association of the CHRNA5/A3/B4 gene cluster with alcohol and cocaine addictions has been reported. Wang et al.52 identified a group of SNPs across CHRNA5/A3 associated with AD. Because these variants are in low linkage disequilibrium (LD) with the SNPs associated with ND and lung cancer, the authors concluded that CHRNA5/A3 variants are associated with AD but through different SNPs and mechanisms from those identified in ND and lung cancer. Moreover, Grucza et al.53 found that a nonsynonymous polymorphism in CHRNA5 has the opposite effect on cocaine dependence (CD) than is associated with ND. Such contradictions in allelic associations are found in other psychiatric disorders also.54 It remains to be seen whether there is true heterogeneity of association (in this case, between ND and CD), or whether some findings will turn out to be false positives.
