Genome-wide association study identifies five loci associated with lung function

Emmanouela Repapi; Ian Sayers; Louise V. Wain; Paul R. Burton; Toby Johnson; Ma'en Obeidat; Jing Hua Zhao; Adaikalavan Ramasamy; Guangju Zhai; Veronique Vitart; Jennifer E. Huffman; Wilmar Igl; Eva Albrecht; Panos Deloukas; John Henderson; Raquel Granell; Wendy L. McArdle; Alicja R. Rudnicka; Ines Barroso; Ruth J. F. Loos; Nicholas J. Wareham; Linda Mustelin; Taina Rantanen; Ida Surakka; Medea Imboden; H. Erich Wichmann; Ivica Grkovic; Stipan Jankovic; Lina Zgaga; Anna-Liisa Hartikainen; Leena Peltonen; Ulf Gyllensten; Asa Johansson; Ghazal Zaboli; Harry Campbell; Sarah H. Wild; James F. Wilson; Sven Glaeser; Georg Homuth; Henry Voelzke; Massimo Mangino; Nicole Soranzo; Tim D. Spector; Ozren Polasek; Igor Rudan; Alan F. Wright; Markku Heliovaara; Samuli Ripatti; Anneli Pouta; Asa Torinsson Naluai; Anna-Carin Olin; Kjell Toren; Matthew N. Cooper; Alan L. James; Lyle J. Palmer; Aroon D. Hingorani; S. Goya Wannamethee; Peter H. Whincup; George Davey Smith; Shah Ebrahim; Tricia M. McKeever; Ian D. Pavord; Andrew K. MacLeod; Andrew D. Morris; David J. Porteous; Cyrus Cooper; Elaine Dennison; Seif Shaheen; Stefan Karrasch; Eva Schnabel; Holger Schulz; Harald Grallert; Nabila Bouatia-Naji; Jerome Delplanque; Philippe Froguel; John D. Blakey; John R. Britton; Richard W. Morris; John W. Holloway; Debbie A. Lawlor; Jennie Hui; Fredrik Nyberg; Marjo-Riitta Jarvelin; Cathy Jackson; Mika Kahonen; Jaakko Kaprio; Nicole M. Probst-Hensch; Beate Koch; Caroline Hayward; David M. Evans; Paul Elliott; David P. Strachan; Ian P. Hall; Martin D. Tobin; Wellcome Trust Case Control Consor

doi:10.1038/ng.501

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Genome-wide association study identifies five loci associated with lung function

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Genome-wide association study identifies five loci associated with lung function

Emmanouela Repapi, Ian Sayers, Louise V. Wain, Paul R. Burton, Toby Johnson, Ma'en Obeidat, Jing Hua Zhao, Adaikalavan Ramasamy, Guangju Zhai, Veronique Vitart, …

Nature genetics, Vol.42(1), pp.36-U51

01/01/2010

DOI: https://doi.org/10.1038/ng.501

PMCID: PMC2862965

PMID: 20010834

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n <= 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

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Title: Genome-wide association study identifies five loci associated with lung function
Creators - without role: Emmanouela Repapi - University of Leicester
Ian Sayers - University of Nottingham
Louise V. Wain - University of Leicester
Paul R. Burton - University of Leicester
Toby Johnson - University of London
Ma'en Obeidat - University of Nottingham
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Adaikalavan Ramasamy - University of London
Guangju Zhai - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Veronique Vitart - College Station Medical Center
Jennifer E. Huffman - College Station Medical Center
Wilmar Igl - Uppsala University
Eva Albrecht - Helmholtz Zentrum München
Panos Deloukas - Wellcome Sanger Institute
John Henderson - University of Bristol
Raquel Granell
Wendy L. McArdle - University of Bristol
Alicja R. Rudnicka - University of London
Ines Barroso - Wellcome Sanger Institute
Ruth J. F. Loos - Massachusetts Rehabilitation Commission
Nicholas J. Wareham - Massachusetts Rehabilitation Commission
Linda Mustelin - University of Helsinki
Taina Rantanen - University of Jyväskylä
Ida Surakka - University of Helsinki
Medea Imboden - University of Zurich
H. Erich Wichmann - Helmholtz Zentrum München
Ivica Grkovic - University of Split
Stipan Jankovic - University of Split
Lina Zgaga - University of Zagreb
Anna-Liisa Hartikainen - University of Oulu
Leena Peltonen - Wellcome Sanger Institute
Ulf Gyllensten - Uppsala University
Asa Johansson - Uppsala University
Ghazal Zaboli - Uppsala University
Harry Campbell - University of Edinburgh
Sarah H. Wild - University of Edinburgh
James F. Wilson - University of Edinburgh
Sven Glaeser - University of Greifswald
Georg Homuth - University of Greifswald
Henry Voelzke - University of Greifswald
Massimo Mangino - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Nicole Soranzo - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Tim D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Ozren Polasek - University of Zagreb
Igor Rudan - University of Split
Alan F. Wright - College Station Medical Center
Markku Heliovaara - Natl Inst Hlth & Welf, Helsinki, Finland
Samuli Ripatti - University of Helsinki
Anneli Pouta - Natl Inst Hlth & Welf, Dept Lifecourse & Serv, Oulu, Finland
Asa Torinsson Naluai - University of Gothenburg
Anna-Carin Olin - University of Gothenburg
Kjell Toren - University of Gothenburg
Matthew N. Cooper - University of Western Australia
Alan L. James - Sir Charles Gairdner Hosp, Dept Pulm Physiol, W Australian Sleep Disorders Res Inst, Perth, WA, Australia
Lyle J. Palmer - University of Western Australia
Aroon D. Hingorani - UCL, Dept Epidemiol & Publ Hlth, London, England
S. Goya Wannamethee - UCL, Dept Primary Care & Populat Hlth, London, England
Peter H. Whincup - University of London
George Davey Smith - University of Bristol
Shah Ebrahim - Supreme Council Of Health
Tricia M. McKeever - University of Nottingham
Ian D. Pavord - Univ Hosp Leicester Natl Hlth Serv Trust, Glenfield Hosp, Inst Lung Hlth, Leicester, Leics, England
Andrew K. MacLeod - University of Edinburgh
Andrew D. Morris - University of Dundee
David J. Porteous - University of Edinburgh
Cyrus Cooper - University of Southampton
Elaine Dennison - University of Southampton
Seif Shaheen - University of London
Stefan Karrasch - Helmholtz Zentrum München
Eva Schnabel - Helmholtz Zentrum München
Holger Schulz - Helmholtz Zentrum München
Harald Grallert - Helmholtz Zentrum München
Nabila Bouatia-Naji - Inst Pasteur, CNRS 8090, Inst Biol, F-59019 Lille, France
Jerome Delplanque - Inst Pasteur, CNRS 8090, Inst Biol, F-59019 Lille, France
Philippe Froguel - Inst Pasteur, CNRS 8090, Inst Biol, F-59019 Lille, France
John D. Blakey - University of Nottingham
John R. Britton
Richard W. Morris - UCL, Dept Primary Care & Populat Hlth, London, England
John W. Holloway - University of Southampton
Debbie A. Lawlor - University of Bristol
Jennie Hui - College Station Medical Center
Fredrik Nyberg - University of Gothenburg
Marjo-Riitta Jarvelin - University of London
Cathy Jackson - University of St Andrews
Mika Kahonen - University of Tampere
Jaakko Kaprio - University of Helsinki
Nicole M. Probst-Hensch - University of Zurich
Beate Koch
Caroline Hayward - College Station Medical Center
David M. Evans
Paul Elliott - University of London
David P. Strachan - University of London
Ian P. Hall - University of Nottingham
Martin D. Tobin - University of Leicester
Wellcome Trust Case Control Consor
Publication Details: Nature genetics, Vol.42(1), pp.36-U51
Publisher: Springer Nature
Number of pages: 10
Grant note: Finnish Ministry of Education National Institute for Health MC_U127561128; MC_U106188470; G0902125; G0801056; MC_U123092720; G0501942; G0401540; G0600331; G0000934; MC_U123092721; G0600705; G0800582 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) St. Thomas' NHS Foundation Trust G0500539; G0501942; G0000943; G990146 / Medical Research Council UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 01GI0883 / German Asthma and COPD Network (COSYCONET) National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) G0801056; MC_U123092720; U1475000001; G0800582; G0600705; G0000934; G0902125; G0600331; G9900991B; G0801056B; G0600717B; MC_U127561128; MC_U106179471; G9815508; MC_U106188470; G0401540; G0501942; MC_U123092721; MC_UP_A620_1014 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) HEFCE Science Research Investment Fund Asthma UK Center of Excellence in Complex Disease Genetics; Research Council of Finland CZD/16/6 / Chief Scientists Office, part of the Scottish Government Health Directorate Helmholtz Zentrum Munchen; Helmholtz Association 01ZZ96030; 01ZZ0701; 01GI0883 / German Federal Ministry of Education and Research (BMBF); Federal Ministry of Education & Research (BMBF) PG/06/154/22043; PG/97012; FS05/125 / British Heart Foundation Healthway, Western Australia International Osteoporosis Foundation Cancer Research United Kingdom; Cancer Research UK NF-SI-0508-10082 / National Institute for Health Research; National Institutes of Health Research (NIHR) AstraZeneca German Research Center for Environmental Health, Neuherberg, Germany National Institute for Health Research comprehensive Biomedical Research Centre; National Institutes of Health Research (NIHR) German National Genome Research Network Biocentrum Helsinki Medical Research Fund of the Tampere University Hospital Arthritis Research Campaign; Versus Arthritis FP-5/QLG1-CT-2000-01643; FP-7/2007-2013; FP-6 LSHB-CT-2006-018996; FP-6 LSHG-CT-2006-01947; HEALTH-F2-2008-201865-GEFOS; QLG2-CT-2002-01254 / European Commission; European Commission Joint Research Centre British Lung Foundation RG/08/013/25942 / British Heart Foundation CZD/16/6/2; CZB/4/710 / Chief Scientist Office Ministry for Social Affairs of the Federal State of Mecklenburg-West Pomerania 0020029 / Department of Health Air Pollution PRP HEALTH-F4-2007-201413 / ENGAGE Biocenter Oulu, University of Oulu National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) German Ministry for Education, Research and Cultural Affairs Juvenile Diabetes Research Foundation International; Juvenile Diabetes Research Foundation Munich Center of Health Sciences, as part of LMUinnovativ National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) 104781; 120315; 1114194 / Academy of Finland; Research Council of Finland Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) Leicester Biomedical Research Unit in Cardiovascular Science (NIHR); National Institutes of Health Research (NIHR) National Human Genome Research Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) MRC Human Genetics Unit; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9937970208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article