In CHRNB3-CHRNA6, evidence suggests that there may be at least two distinct loci associated with nicotine dependence. In this region, the SNP most strongly associated in the full sample is rs13277254, upstream of the gene cluster (2-df p = 0.0021), and this association is driven by the EAs. Some of the additional associated SNPs in this region constitute the same signal because they are very highly correlated with rs13277254. However, the synonymous coding SNP rs4952 in CHRNB3 has the strongest odds ratio in this region (OR = 0.65 (0.47-0.91), p = 0.01 in EAs; OR = 0.42 (0.16-1.08), p = 0.07 in AAs). Rs4952 may tag a distinct involved locus in this gene cluster because it has only low correlation with rs13277254 (r2 = 0.153 in EAs and 0.009 in AAs). The region upstream of the CHRNB3-CHRNA6 cluster has been associated with nicotine dependence and smoking behavior in several European-ancestry samples (Bierut et al., 2007, Ehringer et al., In press, Hoft et al., 2009, Saccone et al., 2009a, Saccone et al., 2007, Zeiger et al., 2008), though the biological implications
