The two most significant SNPs by best model p-value are in the CHRNA5-CHRNA3-CHRNB4 cluster: rs17487223 (best model p = 0.0000266) in CHRNB4 and rs16969968 (best model p = 0.0000284) in CHRNA5. The latter is a non-synonymous SNP in CHRNA5, and we consider it the most biologically promising finding. Both SNPs are in the same r2 bin that includes 7 additional SNPs (5 surpassing the multiple test criterion of 0.000462) extending both upstream into the gene LOC123688 and downstream through CHRNA3 and CHRNB4 (Table II and Figure 2A). These seven SNPs therefore represent a single signal. The additional 4 significant SNPs in the neighboring gene IREB2 form a separate r2 ≥ 0.8 bin but have r2 ≥ 0.68 with rs16969968 (0.78 for rs1504549, 0.694 for rs17405217, 0.690 for rs17484235, 0.697 for rs17483548 0.697, and 0.679 for rs17483686); thus these are still highly correlated and likely constitute the same signal. In this bin, an intronic SNP in IREB2, rs17484235, has a primary p-value of 0.0001244 compared to 0.0001298 for the non-synonymous SNP rs16969968.
