We used independent populations with varying COPD severity, independent genotyping platforms and stringent statistical significance criteria to define genome-wide significant associations. We used consensus criteria for replication using a multi-stage replication design with similar phenotypes, the same genetic model and direction of association [19]. The levels of statistical significance of the association for our most significant results in the CHRNA3/5 region were consistent in all of the populations studied and are unlikely to be false positive results. The p values after adjusting for multiple testing using the most conservative Bonferroni correction were 7.3×10−5 and 2.83×10−4 for the SNPs rs8034191 and rs1051730 respectively. Though this can be considered as strength, the conservative approach for SNP confirmation that we have used may lead to larger false negative rates. However, with the inconsistent results of previous complex disease genetic association studies, we contend that a conservative approach is appropriate. We selected only the top 100 SNPs from the GWAS for subsequent replication study and a larger number of significant associations may have been uncovered if more of the most promising SNPs had been
