During preparation of this article, two other reports of association between variants at the CHRNA5, CHRNA3, and CHRNB4 loci at 15q25 and heavy smoking/nicotine dependence were published [Bierut et al., [2008]; Thorgeirsson et al., [2008]]. These and our study replicated the association of CHRNA5 and CHRNA3 with smoking and nicotine dependence. Two previous studies [Berrettini et al., [2008]; Thorgeirsson et al., [2008]] used the number of cigarettes smoked as phenotype. By contrast, ours and other studies [Saccone et al., [2007]; Bierut et al., [2008]] used FTND as phenotype. To compare directly how much difference the phenotypes made, we examined our data using “the number of maximal cigarettes smoked daily” as a phenotype. In our combined sample, the P-value was 0.0010 (effect = 0.111, 95% CI, 0.045-0.178) for rs16969968, which was comparable with the results obtained with FTND scores (see Table III). But for rs2869546, using the number of cigarettes smoked produced a slightly stronger association (P = 0.0060, effect = 0.092, 95% CI, 0.026-0.159). As pointed out in the previous studies [Saccone et al., [2007]; Berrettini et al., [2008]; Thorgeirsson
