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Chunk #4 — Results — Meta-analyses of CHARGE genome-wide association results

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Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.
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Meta-analyses for FEV1/FVC and FEV1 were conducted using approximately 2,534,500 SNPs in 20,890 CHARGE participants of European ancestry (N=7,980 from ARIC, N=3,140 from CHS, N=7,694 from FHS, N=1,224 from RS-I, and N=852 from RS-II) and in subgroups of ever (N=11,963) and never smokers (N=8,927). Characteristics of the cohort participants are presented in Table 1. We applied genomic control, although cohort-specific genomic inflation factors (λgc) were low (for FEV1/FVC ranging from 1.00 (RS-I and RS-II) to 1.05 (ARIC) and for FEV1 ranging from 1.01 (RS-II) to 1.05 (FHS)) suggesting minimal population stratification. The meta-analysis λgc was 1.04 for FEV1/FVC and 1.03 for FEV1 in all participants. Quantile-quantile (Q-Q) plots show large deviations between observed and expected P values for high-signal SNPs in analyses of FEV1/FVC and FEV1 in all participants (Supplementary Fig. 1a,b), FEV1/FVC in never smokers (Supplementary Fig. 2a), and FEV1 in ever smokers (Supplementary Fig. 3c). Genome-wide significant associations (P<5×10−8) were found for multiple SNPs in each of these analyses (Fig. 1a,b for overall analyses and Supplementary Fig. 2b,d and Supplementary Fig. 3b,d for analyses stratified by ever/never smoking).