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

Research output: Contribution to journalJournal articleResearchpeer-review

Victoria E Jackson, Jeanne C Latourelle, Louise V Wain, Albert V Smith, Megan L Grove, Traci M Bartz, Ma'en Obeidat, Michael A Province, Wei Gao, Beenish Qaiser, David J Porteous, Patricia A Cassano, Tarunveer S Ahluwalia, Niels Grarup, Jin Li, Elisabeth Altmaier, Jonathan Marten, Sarah E Harris, Ani Manichaikul, Tess D Pottinger & 31 others Ruifang Li-Gao, Allan Lind-Thomsen, Anubha Mahajan, Lies Lahousse, Medea Imboden, Alexander Teumer, Bram Prins, Leo-Pekka Lyytikäinen, Gudny Eiriksdottir, Nora Franceschini, Colleen M Sitlani, Jennifer A Brody, Yohan Bossé, Wim Timens, Aldi Kraja, Anu Loukola, Wenbo Tang, Yongmei Liu, Jette Bork-Jensen, Johanne M Justesen, Allan Linneberg, Leslie A Lange, Rajesh Rawal, Stefan Karrasch, Jennifer E Huffman, Blair H Smith, Lars Lind, Charlotta Pisinger, Torben Hansen, Henrik Vestergaard, Understanding Society Scientific Group

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 (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/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.

Original languageEnglish
JournalWellcome Open Research
Volume3
Pages (from-to)1-28
ISSN2398-502X
DOIs
Publication statusPublished - 2018

ID: 204438247