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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

1
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK.
2
Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2RD, UK.
3
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland EH8 9AD, UK.
4
University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6.
5
Generation Scotland, A Collaboration between the University Medical Schools and NHS, Aberdeen, Dundee, Edinburgh, Glasgow EH4 2XU, UK.
6
School of Social and Community Medicine, University of Bristol, Bristol BS8 1TH, UK.
7
Department of Epidemiology and Biostatistics, MRC -PHE Centre for Environment &Health, School of Public Health, Imperial College London, London SW7 2AZ, UK.
8
Busselton Population Medical Research Institute, Busselton, Western Australia 6280, Australia.
9
PathWest Laboratory Medicine WA, Sir Charles Gairdner Hospital, Western Australia 6009, Australia.
10
School of Population Health, The University of Western Australia, Western Australia 6009, Australia.
11
School of Pathology and Laboratory Medicine, The University of Western Australia, Western Australia 6009, Australia.
12
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK.
13
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AD, Scotland, UK.
14
University Medicine Greifswald, Community Medicine, SHIP-Clinical Epidemiological Research, Greifswald 17489, Germany.
15
Department for Genetics and Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17489, Germany.
16
Institute of Genetic Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg D-85764, Germany.
17
Swiss Tropical and Public Health Institute, Basel 4051, Switzerland.
18
University of Basel, Basel 4001, Switzerland.
19
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg D-85764, Germany.
20
Institute of Epidemiology II, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg D-85764, Germany.
21
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9AD, UK.
22
Department of Psychology, University of Edinburgh, Edinburgh EH8 9AD, UK.
23
Department of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, Uppsala 751 23, Sweden.
24
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki FI-00014, Finland.
25
The National Institute for Health and Welfare (THL), Helsinki FI-00271, Finland.
26
Department of Public Health, Faculty of Medicine, University of Split, Split 21000, Croatia.
27
Department of Clinical Chemistry, Fimlab Laboratories, Tampere FI-33101, Finland.
28
Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere FI-33520, Finland.
29
KCL Department of Twins Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK.
30
Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg D-85764, Germany.
31
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
32
Department of Molecular Medicine, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec, Canada G1V 0A6.
33
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen 9700, The Netherlands.
34
Department of Internal Medicine B, Pneumology, Cardiology, Intensive Care, Weaning, Field of Research: Pneumological Epidemiology, University Medicine Greifswald, Greifswald 17489, Germany.
35
Centre for Research in Environmental Epidemiology (CREAL), Barcelona E-08003, Spain.
36
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain.
37
Pompeu Fabra University (UPF), Barcelona 08002, Catalonia, Spain.
38
Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh EH8 9AD, UK.
39
Department of Obstetrics and Gynecology of Oulu University Hospital ,MRC of Oulu University, Oulu 90220, Finland.
40
Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland AB24 3FX, UK.
41
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX1 2JD, UK.
42
Department of Pediatrics, Tampere University Hospital, Tampere 33521, Finland.
43
Department of Pediatrics, University of Tampere School of Medicine, Tampere FI-33520, Finland.
44
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala 751 23, Sweden.
45
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
46
Uppsala Clinical Research Centre, Uppsala University, Uppsala 751 23, Sweden.
47
Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland QLD 4072, Australia.
48
MRC Integrative Epidemiology Unit, Bristol BS8 1TH, UK.
49
Institute of Environmental Medicine, Karolinska Institutet, Stockholm SE-171 7, Sweden.
50
Department of Medical Sciences, Uppsala University, Uppsala 751 23, Sweden.
51
Institute of Environmental Medicine, Karolinska Institutet and Sachs' Children's Hospital, Stockholm SE-171 7, Sweden.
52
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Western Australia 6009, Australia.
53
School of Medicine and Pharmacology, The University of Western Australia, Western Australia 6009, Australia.
54
Genetics and Pharmacogenomics, Merck Research Labs, Boston, Massachusetts 02115, USA.
55
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, UK.
56
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland.
57
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20014, Finland.
58
Department of Public Health, University of Helsinki, Helsinki FI-00014, Finland.
59
Department of Human Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
60
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich 85764, Germany.
61
Respiratory Division, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
62
Alzheimer Scotland Research Centre, University of Edinburgh, Edinburgh EH8 9AD, UK.
63
Department of Medical Biology, Faculty of Medicine, University of Split, Split 21000, Croatia.
64
Respiratory Epidemiology and Public Health, Imperial College London, London SW7 2AZ, UK.
65
MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London SW7 2AZ, UK.
66
Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere 33521, Finland.
67
Centre for Population Health Sciences, Medical School, University of Edinburgh, Edinburgh EH8 9AD, Scotland, UK.
68
Institute of General Practice, University Hospital Klinikum rechts der Isar, Technische Universität München, Munich D - 81675, Germany.
69
Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich 80539, Germany.
70
University Hospital Munich, Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilian University Munich, Munich 80539, Germany.
71
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Western Australia 6009, Australia.
72
Department of Biostatistics, University of Liverpool, Liverpool L69 7ZX, UK.
73
Estonian Genome Centre, University of Tartu, Tartu 50090, Estonia.
74
Center for Life Course Epidemiology, Faculty of Medicine, P.O.Box 5000, FI-90014 University of Oulu, Oulu FI-01051, Finland.
75
Biocenter Oulu, P.O.Box 5000, Aapistie 5A, FI-90014 University of Oulu, Oulu FI-01051, Finland.
76
Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O.Box 20, FI-90220 Oulu, 90029 OYS, Finland.
77
Population Health Research Institute, St George's, University of London, Cranmer Terrace, London WC1B 5DN, UK.
78
National 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
PMCID:
PMC4686825
DOI:
10.1038/ncomms9658
[Indexed for MEDLINE]
Free PMC Article

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