We used a multi-stage replication design (Figure 1) for this study. The genome-wide association analyses of the COPD case-control status in the Bergen cohort identified several significant associations, including three SNPs on chromosome 5 that reached the level of genome-wide significance (Table S1). The Q-Q plot showing the distribution of observed P values from the discovery cohort is shown in online Figure S1. The top 100 SNPs were then evaluated in the ICGN population and 8 were replicated at a nominal p value of 0.05 (SNP rs11219732 showed inconsistent risk alleles in the Bergen and ICGN population and hence was not considered further, Table 2). Two of the three SNPs (rs7727670 and rs7341022 on chromosome 5) that showed genome-wide significance in the Bergen cohort did not replicate in the ICGN population. The SNPs showing the most definitive evidence for replication were rs8034191 and rs1051730 in the CHRNA3/5 locus.
