Meta-analysis of exome array data identifies six novel genetic loci for lung function

Abstract

<p>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.<br />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.<br />Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in <i>RPAP1</i>, which is predicted to be damaging, three intronic SNPs (<i>SEC24C, CASC17 </i>and <i>UQCC1</i>) and two intergenic SNPs near to<i> LY86 </i>and <i>FGF10.</i> Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including <i>TYRO3</i> and <i>PLAU</i>.<br />Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.<br /></p>