Genetic variants in the nicotinic receptor gene cluster on chromosome 15 show important associations with nicotine dependence (13–15). There is evidence of at least two distinct signals in this gene cluster. The most compelling finding is with rs16969968, a non-synonymous coding SNP in exon 5 of CHRNA5, the α5 nicotinic receptor subunit gene which appears to be a functional variant (13). Another SNP, rs3743078, is a proxy for rs578776 in the 3’ UTR of CHRNA3 which has a low correlation with rs16969968 (r2 = 0.15), is also strongly associated with nicotine dependence. These two genetic associations have been replicated in several independent studies (16–20). The same gene cluster on chromosome 15 was also reported to be associated with lung cancer (18, 21–23).
