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Nat Commun. 2015 Dec 4;6:8658. doi: 10.1038/ncomms9658.

Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

Author information

  • 1Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK.
  • 2Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2RD, UK.
  • 3MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland EH8 9AD, UK.
  • 4University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6.
  • 5Generation Scotland, A Collaboration between the University Medical Schools and NHS, Aberdeen, Dundee, Edinburgh, Glasgow EH4 2XU, UK.
  • 6School of Social and Community Medicine, University of Bristol, Bristol BS8 1TH, UK.
  • 7Department of Epidemiology and Biostatistics, MRC -PHE Centre for Environment &Health, School of Public Health, Imperial College London, London SW7 2AZ, UK.
  • 8Busselton Population Medical Research Institute, Busselton, Western Australia 6280, Australia.
  • 9PathWest Laboratory Medicine WA, Sir Charles Gairdner Hospital, Western Australia 6009, Australia.
  • 10School of Population Health, The University of Western Australia, Western Australia 6009, Australia.
  • 11School of Pathology and Laboratory Medicine, The University of Western Australia, Western Australia 6009, Australia.
  • 12MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK.
  • 13Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AD, Scotland, UK.
  • 14University Medicine Greifswald, Community Medicine, SHIP-Clinical Epidemiological Research, Greifswald 17489, Germany.
  • 15Department for Genetics and Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17489, Germany.
  • 16Institute of Genetic Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg D-85764, Germany.
  • 17Swiss Tropical and Public Health Institute, Basel 4051, Switzerland.
  • 18University of Basel, Basel 4001, Switzerland.
  • 19Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg D-85764, Germany.
  • 20Institute of Epidemiology II, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg D-85764, Germany.
  • 21Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9AD, UK.
  • 22Department of Psychology, University of Edinburgh, Edinburgh EH8 9AD, UK.
  • 23Department of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, Uppsala 751 23, Sweden.
  • 24Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki FI-00014, Finland.
  • 25The National Institute for Health and Welfare (THL), Helsinki FI-00271, Finland.
  • 26Department of Public Health, Faculty of Medicine, University of Split, Split 21000, Croatia.
  • 27Department of Clinical Chemistry, Fimlab Laboratories, Tampere FI-33101, Finland.
  • 28Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere FI-33520, Finland.
  • 29KCL Department of Twins Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK.
  • 30Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg D-85764, Germany.
  • 31Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • 32Department of Molecular Medicine, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec, Canada G1V 0A6.
  • 33Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen 9700, The Netherlands.
  • 34Department of Internal Medicine B, Pneumology, Cardiology, Intensive Care, Weaning, Field of Research: Pneumological Epidemiology, University Medicine Greifswald, Greifswald 17489, Germany.
  • 35Centre for Research in Environmental Epidemiology (CREAL), Barcelona E-08003, Spain.
  • 36CIBER Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain.
  • 37Pompeu Fabra University (UPF), Barcelona 08002, Catalonia, Spain.
  • 38Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh EH8 9AD, UK.
  • 39Department of Obstetrics and Gynecology of Oulu University Hospital ,MRC of Oulu University, Oulu 90220, Finland.
  • 40Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland AB24 3FX, UK.
  • 41Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX1 2JD, UK.
  • 42Department of Pediatrics, Tampere University Hospital, Tampere 33521, Finland.
  • 43Department of Pediatrics, University of Tampere School of Medicine, Tampere FI-33520, Finland.
  • 44Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala 751 23, Sweden.
  • 45Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
  • 46Uppsala Clinical Research Centre, Uppsala University, Uppsala 751 23, Sweden.
  • 47Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland QLD 4072, Australia.
  • 48MRC Integrative Epidemiology Unit, Bristol BS8 1TH, UK.
  • 49Institute of Environmental Medicine, Karolinska Institutet, Stockholm SE-171 7, Sweden.
  • 50Department of Medical Sciences, Uppsala University, Uppsala 751 23, Sweden.
  • 51Institute of Environmental Medicine, Karolinska Institutet and Sachs' Children's Hospital, Stockholm SE-171 7, Sweden.
  • 52Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Western Australia 6009, Australia.
  • 53School of Medicine and Pharmacology, The University of Western Australia, Western Australia 6009, Australia.
  • 54Genetics and Pharmacogenomics, Merck Research Labs, Boston, Massachusetts 02115, USA.
  • 55Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, UK.
  • 56Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland.
  • 57Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20014, Finland.
  • 58Department of Public Health, University of Helsinki, Helsinki FI-00014, Finland.
  • 59Department of Human Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • 60Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich 85764, Germany.
  • 61Respiratory Division, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
  • 62Alzheimer Scotland Research Centre, University of Edinburgh, Edinburgh EH8 9AD, UK.
  • 63Department of Medical Biology, Faculty of Medicine, University of Split, Split 21000, Croatia.
  • 64Respiratory Epidemiology and Public Health, Imperial College London, London SW7 2AZ, UK.
  • 65MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London SW7 2AZ, UK.
  • 66Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere 33521, Finland.
  • 67Centre for Population Health Sciences, Medical School, University of Edinburgh, Edinburgh EH8 9AD, Scotland, UK.
  • 68Institute of General Practice, University Hospital Klinikum rechts der Isar, Technische Universität München, Munich D - 81675, Germany.
  • 69Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich 80539, Germany.
  • 70University Hospital Munich, Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilian University Munich, Munich 80539, Germany.
  • 71Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Western Australia 6009, Australia.
  • 72Department of Biostatistics, University of Liverpool, Liverpool L69 7ZX, UK.
  • 73Estonian Genome Centre, University of Tartu, Tartu 50090, Estonia.
  • 74Center for Life Course Epidemiology, Faculty of Medicine, P.O.Box 5000, FI-90014 University of Oulu, Oulu FI-01051, Finland.
  • 75Biocenter Oulu, P.O.Box 5000, Aapistie 5A, FI-90014 University of Oulu, Oulu FI-01051, Finland.
  • 76Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O.Box 20, FI-90220 Oulu, 90029 OYS, Finland.
  • 77Population Health Research Institute, St George's, University of London, Cranmer Terrace, London WC1B 5DN, UK.
  • 78National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.

Abstract

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

PMID:
26635082
[PubMed - in process]
PMCID:
PMC4686825
Free PMC Article
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