Besides the “neutral” or reference haplotype, it has been suggested there are at least 2 other haplotypes with independent effects on CPD in this 15q25 region.2639 Our study confirms previous observations that rs1051730, and tagging SNPs such as rs16969968, exhibit relatively strong effects in this region, and SNPs rs588765 and rs578776, determine independent haplotypes associated with lifetime CPD in COPD patients as well. However, we could not replicate association between lifetime average CPD and rs684513, i.e. the top SNP in the analysis on CPD when conditioning for rs1051730 in the Tobacco and Genetics Consortium.10 Importantly, the effect directions of all candidate SNPs in this 15q25 locus agree with those previously reported, suggesting larger COPD cohorts are required to establish significance of independent SNPs/haplotypes in this region.
