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

Jackson, Victoria E ORCID: 0000-0002-9758-9784, Latourelle, Jeanne C, Wain, Louise V ORCID: 0000-0003-4951-1867, Smith, Albert V, Grove, Megan L, Bartz, Traci M, Obeidat, Ma'en ORCID: 0000-0002-5443-2752, Province, Michael A, Gao, Wei, Qaiser, Beenish
et al (show 97 more authors) (2018) Meta-analysis of exome array data identifies six novel genetic loci for lung function. Wellcome Open Research, 3. 4 - 4.

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<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>

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 08 May 2019 11:35
Last Modified: 16 Sep 2022 04:10
DOI: 10.12688/wellcomeopenres.12583.1
Open Access URL: