Early genetic association studies of nicotine dependence and smoking have looked at some of the nicotinic subunit genes (Greenbaum et al., 2006; Lou et al., 2006), with CHRNA4 and CHRNB2 (coding α4 and β2 respectively) receiving the most attention (Ehringer et al., 2007; Feng et al., 2004; Li et al., 2005; Lou et al., 2007; Lueders et al., 2002; Silverman et al., 2000) until our reports of strong association within the CHRNA5-CHRNA3-CHRNB4 cluster and the CHRNB3-CHRNA6 cluster (Bierut et al., 2007; Saccone et al., 2007a). More recently, our association with rs16969968, a nonsynonymous coding SNP in CHRNA5, has been replicated in several independent datasets using the same SNP (Bierut et al., In press) (Stevens et al., unpublished data) or proxy SNPs having very high r2 with it (Berrettini et al., 2008; Thorgeirsson et al., 2008). Furthermore, this SNP or its r2 proxies have now been associated with lung cancer (Amos et al., 2008; Hung et al., 2008; Thorgeirsson et al., 2008). These findings underscore the nicotinic receptors as important targets for further indepth study.
