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Chunk #29 — Discussion

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Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.
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Population-based cohorts are subject to population stratification, and analytic steps were taken to minimize this potential bias. Cohort-specific λgc values were low (1.00 to 1.05), and a genomic control adjustment was made in the meta-analyses to reduce inflation in the test statistics. The two largest cohorts, with the largest (albeit modest) λgc values (ARIC and FHS), incorporated principal components as potential confounders in their cohort-specific association tests. Although we cannot eliminate the possibility that some findings are subject to residual confounding by population stratification, the Q-Q plots showing deviations between observed and expected P values for many high- to moderate-signal SNPs and the replication of association for multiple top loci in SpiroMeta suggest a multifactorial influence on pulmonary function.