Interestingly, effect sizes of replicated SNPs from the CHRNA3/CHRNA5 locus are similar to most of those from the CYP2A6 locus in our study, which contrasts with recent GWAS where bigger effect sizes were seen for the former locus.8 Additionally, variations in the CHRNA3/CHRNA5, but not CYP2A6, locus showed substantial heterogeneity in genetic effects in our study, and as observed in previous GWAS as well.810 We speculate that this might be due to between-study differences in general (e.g. educational status or peer smoking40) or COPD-specific (e.g. reporting lifetime average CPD which may be influenced by severity of disease) characteristics.
