Meta-analysis of exome array data identifies six novel genetic loci for lung function
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Published:2018-01-12
Issue:
Volume:3
Page:4
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ISSN:2398-502X
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Container-title:Wellcome Open Research
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language:en
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Short-container-title:Wellcome Open Res
Author:
Jackson Victoria E.ORCID, Latourelle Jeanne C., Wain Louise V.ORCID, Smith Albert V., Grove Megan L., Bartz Traci M., Obeidat Ma'enORCID, Province Michael A., Gao Wei, Qaiser Beenish, Porteous David J.ORCID, Cassano Patricia A.ORCID, Ahluwalia Tarunveer S.ORCID, Grarup NielsORCID, Li Jin, Altmaier Elisabeth, Marten JonathanORCID, Harris Sarah E.ORCID, Manichaikul Ani, Pottinger Tess D.ORCID, Li-Gao RuifangORCID, Lind-Thomsen Allan, Mahajan AnubhaORCID, Lahousse LiesORCID, Imboden Medea, Teumer AlexanderORCID, Prins Bram, Lyytikäinen Leo-PekkaORCID, Eiriksdottir Gudny, Franceschini Nora, Sitlani Colleen M.ORCID, Brody Jennifer A.ORCID, Bossé YohanORCID, Timens WimORCID, Kraja Aldi, Loukola Anu, Tang Wenbo, Liu Yongmei, Bork-Jensen Jette, Justesen Johanne M.ORCID, Linneberg AllanORCID, Lange Leslie A., Rawal Rajesh, Karrasch Stefan, Huffman Jennifer E., Smith Blair H.ORCID, Davies Gail, Burkart Kristin M., Mychaleckyj Josyf C.ORCID, Bonten Tobias N., Enroth StefanORCID, Lind Lars, Brusselle Guy G., Kumar Ashish, Stubbe Beate, Kähönen MikaORCID, Wyss Annah B., Psaty Bruce M., Heckbert Susan R., Hao Ke, Rantanen TainaORCID, Kritchevsky Stephen B.ORCID, Lohman Kurt, Skaaby Tea, Pisinger Charlotta, Hansen Torben, Schulz Holger, Polasek Ozren, Campbell Archie I.ORCID, Starr John M., Rich Stephen S., Mook-Kanamori Dennis O., Johansson Åsa, Ingelsson Erik, Uitterlinden André G., Weiss StefanORCID, Raitakari Olli T., Gudnason Vilmundur, North Kari E., Gharib Sina A.ORCID, Sin Don D.ORCID, Taylor Kent D.ORCID, O'Connor George T., Kaprio JaakkoORCID, Harris Tamara B., Pederson Oluf, Vestergaard HenrikORCID, Wilson James G., Strauch Konstantin, Hayward CarolineORCID, Kerr Shona M.ORCID, Deary Ian J.ORCID, Barr R. Graham, de Mutsert Renée, Gyllensten Ulf, Morris Andrew P.ORCID, Ikram M. Arfan, Probst-Hensch Nicole, Gläser Sven, Zeggini Eleftheria, Lehtimäki Terho, Strachan David P., Dupuis Josée, Morrison Alanna C., Hall Ian P.ORCID, Tobin Martin D.ORCID, London Stephanie J.ORCID,
Abstract
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 (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. 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.
Funder
Medical Research Council National Heart, Lung, and Blood Institute National Center for Advancing Translational Sciences Leids Universitair Medisch Centrum U.S. Department of Health and Human Services National Institutes of Health National Institute of Nursing Research Wellcome Trust The Vleugels Foundation Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging National Institute of Environmental Health Sciences The Åke Wiberg foundation Centre National de Génotypage Swedish Heart-Lung Foundation Dutch Science Organisation Federal State of Mecklenburg-West Pomerania National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center Ministry of Science, Education and Sports of the Republic of Croatia Knut och Alice Wallenberg Foundation Swiss National Science Foundation Scottish Funding Council Age UK National Center for Advancing Translation Studies The Marcus Borgström Foundation Academy of Finland Economic and Social Research Council National Institute on Aging Scottish Government Health Directorates Swedish Research Council US Environmental Protection Agency Swedish Society for Medical Research The Royal Society of Edinburgh European Commission FP6 Federal Ministry of Education and Research The Kjell och Märta Beijers Foundation Netherlands Organization for Scientific Research Research Institute for Diseases in the Elderly
Publisher
F1000 Research Ltd
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Cited by
8 articles.
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