The initial GWAS in COPD found significant associations on chromosome 15q25, with SNPs in the genes CHRNA3 and CHRNA5, encoding two subunits of the nicotinic acetylcholine receptor [12]. This region has also been associated with lung cancer, peripheral arterial disease, and smoking behavior [37], [40]–[43], so it is not clear whether these genes have a direct effect on COPD susceptibility, or their effects are at least partially influenced through cigarette smoking, the major environmental risk factor for COPD [44], [45]. In terms of genetic regulation of expression of the chromosome 15q25 genes, we found similar eQTL associations with CHRNA5 expression in induced sputum as has been found in brain [38] and lung tissue [39]. We found additional sputum eQTL SNPs for CHRNA5 in moderate LD with previously defined eQTLs. The previous papers on brain and lung tissue gene expression did not report testing IREB2, a gene previously associated with COPD [11], [36]. The specific IREB2 SNPs associated in GWAS (rs13180) [11] and in a candidate gene analysis of differentially expressed genes (rs2656069) [36] were in only moderate LD (r2 =
