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 (p = 1.1×10−4, OR 1.34 (1.16-1.56)) have comparable evidence and effect size for association. In contrast, (Hung et al., 2008) typed both SNPs in the discovery subset of their sample and in that subsample found lung cancer association p-values of 5×10−9 (OR 1.32 (1.2-1.44)) for rs16969968 versus 2.5×10−4 (OR 1.2 (1.08-1.33)) for rs578776. Future work to clarify the direct versus indirect effects of these variants on lung cancer will be of great interest.
