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

Abstract

<ns4:p> <ns4:bold>Background:</ns4:bold> 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. </ns4:p> <ns4:p> <ns4:bold>Methods:</ns4:bold> We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV <ns4:sub>1</ns4:sub> ), forced vital capacity (FVC) and the ratio of FEV <ns4:sub>1</ns4:sub> to FVC (FEV <ns4:sub>1</ns4:sub> /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. </ns4:p> <ns4:p> <ns4:bold>Results:</ns4:bold> We identified significant (P&lt;2·8x10 <ns4:sup>-7</ns4:sup> ) associations with six SNPs: a nonsynonymous variant in <ns4:italic>RPAP1</ns4:italic> , which is predicted to be damaging, three intronic SNPs ( <ns4:italic>SEC24C, CASC17</ns4:italic> and <ns4:italic>UQCC1</ns4:italic> ) and two intergenic SNPs near to <ns4:italic>LY86</ns4:italic> and <ns4:italic>FGF10.</ns4:italic> Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including <ns4:italic>TYRO3</ns4:italic> and <ns4:italic>PLAU</ns4:italic> . </ns4:p> <ns4:p> <ns4:bold>Conclusions:</ns4:bold> Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease. </ns4:p>