Abstract
Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
Highlights
Measures of lung function act as predictors of mortality and morbidity and form the basis for the diagnosis of several diseases, most notably chronic obstructive pulmonary disease (COPD), one of the leading causes of death globally[1]
We carried out a meta-analysis of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC)
All studies are listed with their study-specific sample characteristics in Table 1, with full study descriptions, including details of spirometry and other measurements described in the Supplementary Note
Summary
Measures of lung function act as predictors of mortality and morbidity and form the basis for the diagnosis of several diseases, most notably chronic obstructive pulmonary disease (COPD), one of the leading causes of death globally[1]. Genomewide association studies (GWAS) of lung function have identified associations between single nucleotide polymorphisms (SNPs) and lung function at over 150 independent loci to date[6,7,8,9,10,11,12,13,14]. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease
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