Human imaging studies indicate that nicotine from a single cigarette nearly completely saturates α4β2 nAChRs (35), and abstinence from nicotine is associated with an increase in the number of unbound β2-containing nAChRs, and thus increasing urge to smoke (36). Based on these observations, genes encoding nAChR subunits have been a focus of a number of previous genetic studies of nicotine dependence. A recent study reported associations of initial subjective responses to nicotine with an SNP immediately upstream of CHRNB2 and one of the two 3′ UTR SNPs (rs2072660) identified by the present study (37). Other candidate gene studies that have examined one or both of the two CHRNB2 3′ UTR SNPs, along with additional SNPs in CHRNB2, have not found association with nicotine dependence at CHRNB2 (15,38–40) in a variety of community- and population-based samples of smokers. In addition, an analysis using smokers and non-smokers that included the two CHRNB2 3′ UTR SNPs and rs2236196 at CHRNA4 to detect gene–gene interactions associated with nicotine dependence failed to detect significant interaction (41). However, nicotine dependence only modestly predicts smoking cessation in
