Four candidate SNPs (rs7251570, rs4105144, rs1801272 and rs12461383) in the CYP2A6 locus on chromosome 19q13 were significantly (p<0.05) associated with lifetime average CPD with the same direction of effect as seen in previous GWAS on CPD (table 2). A non-synonymous SNP (rs1801272) was the second most significantly associated SNP in this locus (figure 2, table 2). There is, at most, a moderate level of LD between these 4 SNPs according to the HapMap phase II panel (r2≤0.6 and D’≥0.84, see online supplementary figure 3). Analysis of proxy SNPs that were genotyped in at least three cohorts was performed. Analysis of rs8102683 (genotyped in the NETT, ECLIPSE and Norwegian cohorts, and imputed in COPDGene) that is a proxy for rs4105144 (r2=0.87), and rs7251418 (genotyped in all cohorts) that is a proxy for rs7251570 (r2=0.81) confirmed the associations observed (p= 4.65×10−5 (B=0.074 for the “C” effect allele; I2=0) and p=0.0024 (B=0.054 for the “G” effect allele; I2=0), respectively). No genotyped proxy SNPs could be found for rs12461383 and rs1801272 SNPs. We did not replicate, with a nominal p<0.05, associations between SNPs in
