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Chunk #15 — Results — Associations in individuals with normal pulmonary function

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Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.
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To address whether the genetic associations hold even among people with normal pulmonary function, we repeated the meta-analyses after excluding individuals with asthma or COPD, leaving 17,855 individuals (N=6,912 from ARIC, N=2,634 from CHS, N=6,371 from FHS, N=1,126 from RS-I, and N=812 from RS-II). Asthma was defined by self-report of ever having asthma or self-report of ever having physician-diagnosed asthma. COPD was defined spirometrically as having both FEV1/FVC and FEV1 less than the lower limit of normal values using NHANES III prediction equations18,19. Comparing the original meta-analyses to the meta-analyses with exclusions for asthma and COPD, β estimates were highly correlated for the high-signal SNPs tested for replication (Pearson’s r>0.99 for 18 FEV1/FVC SNPs and 12 FEV1 SNPs). β estimates remained highly correlated for SNPs with P values as high as 0.01 in the original meta-analyses (r=0.92 for FEV1/FVC and r=0.96 for FEV1). As expected, there was some attenuation in P values for many of the SNPs in our implicated loci given the substantial power loss due to both reduced sample size and the truncation of the FEV1/FVC and FEV1