The variants rs16969968, a non-synonymous coding SNP in CHRNA5, and rs1051730, a synonymous SNP, are of particular interest because these SNPs are strongly associated with nicotine dependence and smoking behaviors (Amos et al. 2008; Berrettini et al. 2008; Liu et al. 2010; Thorgeirsson et al. 2008; Thorgeirsson et al. 2010; Tobacco and Genetics Consortium 2010). These two SNPs are highly correlated (r2 = 0.991) in our data, and we included rs16969968 in our list of 127 to be tested. We selected this SNP because it results in an amino acid change, and in vitro studies demonstrate that it alters receptor function (Bierut et al. 2008). Because SNPs were thinned to include only those with r2 < 0.95, rs1051730 was not included in our primary analyses. We confirmed, with secondary univariate and joint analyses using rs1051730, that the results were very similar to those for rs16969968. (An analog of Table 2, replacing rs16969968 throughout with rs1061730, can be found in Supplemental Table S2.) We cannot say which, if either, of these two SNPs is biologically linked to smoking behavior. We can
