Genome-wide association study of lung function decline in adults with and without asthma.
In: ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://inserm.hal.science/inserm-00744741 ; Journal of Allergy and Clinical Immunology, 2012, 129 (5), pp.1218-28. ⟨10.1016/j.jaci.2012.01.074⟩, 2012
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Zugriff:
International audience ; BACKGROUND: Genome-wide association studies have identified determinants of chronic obstructive pulmonary disease, asthma, and lung function level; however, none have addressed decline in lung function. OBJECTIVE: We conducted the first genome-wide association study on the age-related decrease in FEV(1) and its ratio to forced vital capacity (FVC) stratified a priori by asthma status. METHODS: Discovery cohorts included adults of European ancestry (1,441 asthmatic and 2,677 nonasthmatic participants: the Epidemiological Study on the Genetics and Environment of Asthma, the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, and the European Community Respiratory Health Survey). The associations of FEV(1) and FEV(1)/FVC ratio decrease with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed up by in silico replication (1,160 asthmatic and 10,858 nonasthmatic participants: Atherosclerosis Risk in Communities, the Framingham Heart Study, the British 1958 Birth Cohort, and the Dutch Asthma Study). RESULTS: Main signals identified differed between asthmatic and nonasthmatic participants. None of the SNPs reached genome-wide significance. The association between the height-related gene DLEU7 and FEV(1) decrease suggested for nonasthmatic participants in the discovery phase was replicated (discovery, P = 4.8 × 10(-6); replication, P = .03), and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, which is associated with FEV(1)/FVC ratio decrease in asthmatic participants (P = 5.3 × 10(-8)), did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline. CONCLUSIONS: Genetic heterogeneity of lung function might be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status.
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Genome-wide association study of lung function decline in adults with and without asthma.
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| Autor/in / Beteiligte Person: | Imboden, Medea ; Bouzigon, Emmanuelle ; Curjuric, Ivan ; Ramasamy, Adaikalavan ; Kumar, Ashish ; Hancock, Dana, B. ; Wilk, Jemma, B. ; Vonk, Judith, M. ; Thun, Gian, A. ; Siroux, Valerie ; Nadif, Rachel ; Monier, Florent ; Gonzalez, Juan, R. ; Wjst, Matthias ; Heinrich, Joachim ; Loehr, Laura, R. ; Franceschini, Nora ; North, Kari, E. ; Altmüller, Janine ; Koppelman, Gerard, H. ; Guerra, Stefano ; Kronenberg, Florian ; Lathrop, Mark ; Moffatt, Miriam, F. ; O'Connor, George, T. ; Strachan, David, P. ; Postma, Dirkje, S. ; London, Stephanie, J. ; Schindler, Christian ; Kogevinas, Manolis ; Kauffmann, Francine ; Jarvis, Debbie, L. ; Demenais, Florence ; Probst-Hensch, Nicole, M. ; Epidemiology & Public Health ; Swiss Tropical and Public Health Institute Basel -Medical School University of Basel ; Centre d'Etude du Polymorphisme Humain (CEPH) ; Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH) ; Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset ; Variabilité Génétique et Maladies Humaines (U946) ; Institut Universitaire d'Hématologie (IUH) ; Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Respiratory Epidemiology and Public Health ; Imperial College London-School of public health ; The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health ; The Wellcome Trust Centre for Human Genetics Oxford ; University of Oxford ; Department of Health and Human Services ; National Institutes of Health Bethesda, MD, USA (NIH) ; Behavioral Health Epidemiology Program ; Research Triangle Institute International (RTI International) ; Departments of Neurology and Medicine ; Boston University School of Medicine (BUSM) ; Boston University Boston (BU)-Boston University Boston (BU)-Pulmonary Center, Department of Medicine ; Pediatric Pulmonology, Allergology & Epidemiology ; University of Groningen Groningen -University Medical Center Groningen Groningen (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and, COPD ; Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823) ; Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Centre de recherche en épidémiologie et santé des populations (CESP) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Center for Research in Environmental Epidemiology (CREAL) ; Universitat Pompeu Fabra Barcelona (UPF)-Catalunya ministerio de salud ; IMIM-Hospital del Mar ; Generalitat de Catalunya = Generalidad de Cataluña = Government of Catalonia ; Institute of Epidemiology Neuherberg (EPI) ; German Research Center for Environmental Health - Helmholtz Center München (GmbH) ; Department of Epidemiology ; University of North Carolina Chapel Hill (UNC) ; University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences ; Cologne Center for Genomics (CCG) ; Cologne Center for Genomics-University of Cologne ; Arizona Respiratory Center ; Division of genetic epidemiology ; HMNC Brain Health-Molecular and Clinical Pharmacology-Innsbruck Medical University = Medizinische Universität Innsbruck (IMU) ; Centre National de Génotypage (CNG) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA) ; Institut de Génomique d'Evry (IG) ; Université Paris-Saclay-Institut de Biologie François JACOB (JACOB) ; Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) ; National Heart and Lung Institute (NHLI) ; Imperial College London ; National Heart, Lung, and Blood Institute Bethesda (NHLBI) ; Population Health Sciences and Education ; St George's University of London ; Epidemiology ; National School of Public Health-Medical School of Athens ; EGEA: INSERM-Ministry of Research 'Cohortes et Collections' grant (4CH06G). French Ministry of Higher Education and Research, University Paris Diderot-Paris 7, grants from the French Agency for Environmental and Occupational Health Safety (grant AFSSETAPR- SE-2004), the French National Agency for Research (grants ANR 05- SEST-020- 02/05-9-97 and ANR 06-CEBS), PHRC-Paris, Merck Sharp & Dohme (MSD)) SAPALDIA: Swiss National Science Foundation (grants no 4026-28099,3347CO- 108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 32-65896.01,32- 59302.99, 32-52720.97, 32-4253.94) ; the Federal Office for Forest, Environment and Landscape ; the Federal Office of Public Health ; the Federal Office of Roads and Transport ; the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Zurich ; the Swiss Lung League ; the canton's Lung League of Basel Stadt/ Basel Landschaft, Geneva, Ticino and Zurich ; Freie Akademische Gesellschaft (FAG) ; UBS Wealth Foundation. ECRHS: The co-ordination of ECRHS II was supported by the European Commission, as part of their Quality of Life programme. The following bodies funded the local studies in ECRHS II: Albacete: Fondo de Investigaciones Santarias (FIS) (grant code: 97/0035-01, 99/0034-01 and 99/0034-02), Hospital Universitario de Albacete, Consejeria de Sanidad ; Barcelona: SEPAR, Public Health Service (grant code: R01 HL62633-01), Fondo de Investigaciones Santarias (FIS) (grant code: 97/0035-01, 99/0034-01 and 99/0034-02) CIRIT (grant code: 1999SGR 00241) Red Respira ISCII ; CIBER Epidemiologia y Salud Pública (CIBERESP), Spain Basel: Swiss National Science Foundation, Swiss Federal Office for Education & Science, Swiss National Accident Insurance Fund (SUVA), USC NIEHS Center grant 5P30 ES07048 ; Bergen: Norwegian Research Council, Norwegian Asthma & Allergy Association (NAAF), Glaxo Wellcome AS, Norway Research Fund ; Erfurt: GSF-National Research Centre for Environment & Health, Deutsche Forschungsgemeinschaft (DFG) (grant code FR 1526/1-1) ; Galdakao: Basque Health Dept ; Grenoble: Programme Hospitalier de Recherche Clinique-DRC de Grenoble 2000 no. 2610, Ministry of Health, Direction de la Recherche Clinique, CHU de Grenoble, Ministere de l'Emploi et de la Solidarite, Direction Generale de la Sante, Comite des Maladies Respiratoires de l'Isere ; Hamburg: GSF-National Reasearch Centre for Environment & Health, Deutsche Forschungsgemeinschaft (DFG) (grant code MA 711/4-1) ; Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign) ; Huelva: Fondo de Investigaciones Santarias (FIS) (grant code: 97/0035-01, 99/0034-01 and 99/0034-02) ; Oviedo: Fondo de Investigaciones Santarias (FIS) (grant code: 97/0035-01, 99/0034-01 and 99/0034-02) ; Paris: Ministere de l'Emploi et de la Solidarite, Direction Generale de la Sante, UCB-Pharma (France), Aventis (France), Glaxo France, Programme Hospitalier de Recherche Clinique-DRC de Grenoble 2000 no. 2610, Ministry of Health, Direction de la Recherche Clinique, CHU de Grenoble ; Tartu: Estonian Science Foundation ; Umeå: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences & Allergy Research, Swedish Asthma & Allergy Foundation, Swedish Cancer & Allergy Foundation ; Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences & Allergy Research, Swedish Asthma & Allergy Foundation, Swedish Cancer & Allergy Foundation ; Financial support for ECRHS I for centres in ECRHS II was provided by: Ministère de la Santé, Glaxo France, Insitut Pneumologique d'Aquitaine, Contrat de Plan Etat-Région Languedoc-Rousillon, CNMATS, CNMRT (90MR/10, 91AF/6), Ministre delegué de la santé, RNSP, France ; GSF, and the Bundesminister für Forschung und Technologie, Bonn, Germany ; Norwegian Research Council project no. 101422/310 ; Ministero Sanidad y Consumo FIS (grants #91/0016060/00E-05E and #93/0393), and grants from Hospital General de Albacete, Hospital General Juan Ramón Jiménenz, Consejeria de Sanidad Principado de Asturias, Spain ; The Swedish Medical Research Council, the Swedish Heart Lung Foundation, the Swedish Association against Asthma and Allergy ; Swiss National Science Foundation grant 4026-28099 ; National Asthma Campaign, British Lung Foundation, Department of Health, South Thames Regional Health Authority, UK. A.R. was supported by the Department of Health, UK and the European Commission as part of GABRIEL contract number 018996 under the Integrated Program LSH-2004-1.2.5-1. Genotyping of the discovery cohort and part of B58C was funded by the GABRIEL asthma genetic consortium supported by a contract from the European Commission(018996) and grants from the French Ministry of Research, the Wellcome Trust (WT084703MA), and Asthma UK. Replication cohorts: ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694 ; National Human Genome Research Institute contract U01HG004402 ; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Work for this manuscript was supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS, Z01ES043012). FHS: National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). Dr. Wilk by a Young Clinical Scientist Award from the Flight Attendant Medical Research Institute (FAMRI). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. B58C: British 1958 Birth Cohort was funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02 (http://www.b58cgene.sgul.ac.uk/). Genotyping was funded by the Wellcome Trust grant 076113/B/04/Z, by the United States National Institutes of Health and the Juvenile Diabetes Research Foundation U01 DK062418 and by the European Commission Framework Programme 6 (018996). Dutch Asthma Study: The Dutch Asthma study has been funded by the Netherlands Asthma Foundation grants AF 3.2.07.015 ; and AF 98.48 and a grant from the University Medical Center Groningen |
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| Zeitschrift: | ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://inserm.hal.science/inserm-00744741 ; Journal of Allergy and Clinical Immunology, 2012, 129 (5), pp.1218-28. ⟨10.1016/j.jaci.2012.01.074⟩, 2012 |
| Veröffentlichung: | HAL CCSD ; Elsevier, 2012 |
| Medientyp: | academicJournal |
| DOI: | 10.1016/j.jaci.2012.01.074 |
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