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<ns5:p><ns5:bold>Background:</ns5: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.</ns5:p><ns5:p> <ns5:bold>Methods:</ns5:bold> We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV<ns5:sub>1</ns5:sub>), forced vital capacity (FVC) and the ratio of FEV<ns5:sub>1</ns5:sub> to FVC (FEV<ns5:sub>1</ns5: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.</ns5:p><ns5:p> <ns5:bold>Results:</ns5:bold> We identified significant (P<2·8x10<ns5:sup>-7</ns5:sup>) associations with six SNPs: a nonsynonymous variant in <ns5:italic>RPAP1</ns5:italic>, which is predicted to be damaging, three intronic SNPs (<ns5:italic>SEC24C, CASC17 </ns5:italic>and <ns5:italic>UQCC1</ns5:italic>) and two intergenic SNPs near to<ns5:italic> LY86 </ns5:italic>and <ns5:italic>FGF10.</ns5:italic> Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including <ns5:italic>TYRO3</ns5:italic> and <ns5:italic>PLAU</ns5:italic>.</ns5:p><ns5:p> <ns5:bold>Conclusions: </ns5:bold>Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.</ns5:p>

Original publication

DOI

10.12688/wellcomeopenres.12583.3

Type

Journal article

Publication Date

07/08/2018

Keywords

Understanding Society Scientific Group