Those reports differed in their interpretation of this association with lung cancer — that is, whether it is evidence of a direct effect on lung cancer vulnerability, or whether it can be explained entirely through the indirect effect of increased risk for smoking. What is clear is that this locus is a risk factor for nicotine dependence and smoking quantity. However, it is interesting to note that for lung cancer, the odds ratios for the effect of one copy of the risk allele were 1.30 (95% confidence interval 1.23-1.38) for rs16969968 (Hung et al., 2008), 1.32 (1.24-1.41) for rs8034191 and 1.32 (1.23-1.39) for rs1051730 (Amos et al., 2008), and 1.31 (1.19-1.44) for rs1051730 (Thorgeirsson et al., 2008). These therefore match the odds ratio we see for nicotine dependence: 1.31 (1.14-1.5) for rs16969968. The lung cancer studies highlighted this single risk locus in this region, and appear to indicate weaker association between lung cancer and rs578776, which tags our second nicotine dependence locus in the CHRNA5-CHRNA3-CHRNB4 cluster. In our nicotine dependence study, rs16969968 (p = 1.3×10−4, OR 1.31 (1.14-1.5)) and rs578776
