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Nat Genet. 2014 Jul;46(7):669-77. doi: 10.1038/ng.3011. Epub 2014 Jun 15.

Genome-wide association analysis identifies six new loci associated with forced vital capacity.

Loth DW1, Soler Artigas M2, Gharib SA3, Wain LV2, Franceschini N4, Koch B5, Pottinger TD6, Smith AV7, Duan Q8, Oldmeadow C9, Lee MK10, Strachan DP11, James AL12, Huffman JE13, Vitart V13, Ramasamy A14, Wareham NJ15, Kaprio J16, Wang XQ17, Trochet H13, Kähönen M18, Flexeder C19, Albrecht E20, Lopez LM21, de Jong K22, Thyagarajan B23, Alves AC24, Enroth S25, Omenaas E26, Joshi PK27, Fall T28, Viñuela A29, Launer LJ30, Loehr LR31, Fornage M32, Li G33, Wilk JB34, Tang W35, Manichaikul A36, Lahousse L37, Harris TB30, North KE38, Rudnicka AR11, Hui J39, Gu X32, Lumley T40, Wright AF13, Hastie ND13, Campbell S13, Kumar R41, Pin I42, Scott RA15, Pietiläinen KH43, Surakka I44, Liu Y45, Holliday EG9, Schulz H19, Heinrich J46, Davies G47, Vonk JM22, Wojczynski M48, Pouta A49, Johansson A50, Wild SH27, Ingelsson E51, Rivadeneira F52, Völzke H53, Hysi PG29, Eiriksdottir G54, Morrison AC55, Rotter JI56, Gao W57, Postma DS58, White WB59, Rich SS60, Hofman A61, Aspelund T62, Couper D63, Smith LJ41, Psaty BM64, Lohman K65, Burchard EG66, Uitterlinden AG67, Garcia M30, Joubert BR68, McArdle WL69, Musk AB70, Hansel N71, Heckbert SR72, Zgaga L73, van Meurs JB52, Navarro P13, Rudan I27, Oh YM74, Redline S75, Jarvis DL76, Zhao JH15, Rantanen T77, O'Connor GT78, Ripatti S79, Scott RJ9, Karrasch S80, Grallert H81, Gaddis NC82, Starr JM83, Wijmenga C84, Minster RL85, Lederer DJ86, Pekkanen J87, Gyllensten U25, Campbell H27, Morris AP88, Gläser S89, Hammond CJ29, Burkart KM90, Beilby J39, Kritchevsky SB91, Gudnason V62, Hancock DB92, Williams OD93, Polasek O94, Zemunik T95, Kolcic I94, Petrini MF96, Wjst M97, Kim WJ98, Porteous DJ99, Scotland G100, Smith BH101, Viljanen A77, Heliövaara M102, Attia JR9, Sayers I103, Hampel R104, Gieger C20, Deary IJ21, Boezen HM22, Newman A105, Jarvelin MR106, Wilson JF27, Lind L107, Stricker BH108, Teumer A109, Spector TD29, Melén E110, Peters MJ52, Lange LA111, Barr RG86, Bracke KR112, Verhamme FM112, Sung J113, Hiemstra PS114, Cassano PA115, Sood A116, Hayward C117, Dupuis J118, Hall IP119, Brusselle GG120, Tobin MD2, London SJ121.

Author information

1
1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Health Care Inspectorate, The Hague, the Netherlands. [3].
2
1] Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK. [3].
3
1] Computational Medicine Core, Center for Lung Biology, University of Washington, Seattle, Washington, USA. [2] Department of Medicine, University of Washington, Seattle, Washington, USA. [3].
4
1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [3].
5
1] Department of Internal Medicine B-Pneumology, Cardiology, Intensive Care and Infectious Diseases, University Hospital Greifswald, Greifswald, Germany. [2].
6
1] Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA. [2].
7
1] Iceland Heart Association, Kopavogur, Iceland. [2] University of Iceland, Reykjavik, Iceland. [3].
8
1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [2].
9
1] Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia. [2] Faculty of Health, University of Newcastle, Newcastle, New South Wales, Australia.
10
Institute of Health and Environment, Seoul National University, Seoul, South Korea.
11
Division of Population Health Sciences and Education, St George's, University of London, London, UK.
12
1] Department of Pulmonary Physiology and Sleep Medicine/West Australian Sleep Disorders Research Institute, Nedlands, Western Australia, Australia. [2] School of Medicine and Pharmacology, The University of Western Australia, Perth, Western Australia, Australia. [3] Busselton Population Medical Research Institute, Busselton, Western Australia, Australia.
13
Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, UK.
14
1] Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College London, London, UK. [2] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
15
MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
16
1] Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare (THL), Helsinki, Finland. [3] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
17
Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
18
Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
19
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
20
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
21
1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. [2] Department of Psychology, University of Edinburgh, Edinburgh, UK.
22
1] Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. [2] Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
23
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
24
Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
25
1] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
26
1] Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway. [2] Department of Clinical Sciences, University of Bergen, Bergen, Norway.
27
Centre for Population Health Sciences, Medical School, University of Edinburgh, Edinburgh, UK.
28
1] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [2] Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
29
Department of Twins Research and Genetic Epidemiology, King's College London, London, UK.
30
Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
31
1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
32
1] Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA. [2] Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.
33
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
34
Precision Medicine, Pfizer Global Research and Development, Cambridge, Massachusetts, USA.
35
Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
36
1] Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA. [2] Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
37
1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
38
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
39
PathWest Laboratory Medicine Washington, Nedlands, Western Australia, Australia.
40
Department of Statistics, University of Auckland, Auckland, New Zealand.
41
Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
42
1] Centre Hospitalier Universitaire de Grenoble, Grenoble, France. [2] INSERM U823, Institut Albert Bonniot, Grenoble, France. [3] Université Joseph Fourier, Grenoble, France.
43
1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. [3] Division of Internal Medicine, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
44
1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland.
45
Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
46
1] Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] Comprehensive Pneumology Center Munich (CPC-M), member of the German Center for Lung Research, Munich, Germany.
47
1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. [2] Department of Psychology, University of Edinburgh, Edinburgh, UK. [3] Medical Genetics Section, Centre for Genomics and Experimental Medicine, MRC IGMM, University of Edinburgh, Edinburgh, UK. [4] MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.
48
Department of Statistical Genomics, Washington University, St. Louis, Missouri, USA.
49
1] National Institute for Health and Welfare, Oulu, Finland. [2] Department of Clinical Sciences/Obstetrics and Gynecology, University Hospital of Oulu, University of Oulu, Oulu, Finland.
50
1] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [3] Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
51
1] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [2] Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
52
1] Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
53
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
54
Iceland Heart Association, Kopavogur, Iceland.
55
School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.
56
1] Biomedical Research Institute, Harbor-University of California, Los Angeles (UCLA) Medical Center, Torrance, California, USA. [2] Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
57
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
58
1] Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. [2] Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
59
Tougaloo College, Jackson, Mississippi, USA.
60
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
61
1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
62
1] Iceland Heart Association, Kopavogur, Iceland. [2] University of Iceland, Reykjavik, Iceland.
63
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
64
1] Department of Medicine, University of Washington, Seattle, Washington, USA. [2] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA. [3] Department of Epidemiology, University of Washington, Seattle, Washington, USA. [4] Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
65
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
66
1] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. [2] Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
67
1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. [3] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
68
Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
69
School of Social and Community Medicine, University of Bristol, Bristol, UK.
70
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
71
Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
72
1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA. [3] Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
73
1] Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland. [2] Adrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia.
74
1] Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. [2] Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
75
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
76
1] Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College London, London, UK. [2] MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
77
Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
78
1] Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
79
1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland. [3] Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, UK.
80
1] Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig Maximilians Universität, Munich, Germany. [3] Institute of General Practice, University Hospital Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
81
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
82
Research Computing Division, Research Triangle Institute International, Research Triangle Park, North Carolina, USA.
83
1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. [2] Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
84
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
85
Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
86
1] Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA. [2] Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
87
1] Department of Environmental Health, National Institute for Health and Welfare (THL), Kuopio, Finland. [2] Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
88
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
89
Department of Internal Medicine B-Pneumology, Cardiology, Intensive Care and Infectious Diseases, University Hospital Greifswald, Greifswald, Germany.
90
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
91
Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
92
1] Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA. [2] Behavioral Health Epidemiology Program, Research Triangle Institute International, Research Triangle Park, North Carolina, USA.
93
Florida International University, Miami, Florida, USA.
94
Department of Public Health, Medical School, University of Split, Split, Croatia.
95
Department of Medical Biology, Medical School, University of Split, Split, Croatia.
96
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
97
Comprehensive Pneumology Center (CPC), Helmholtz Zentrum München (HMGU), Munich, Germany.
98
1] Department of Internal Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, South Korea. [2] Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, South Korea.
99
Medical Genetics Section, Centre for Genomics and Experimental Medicine, MRC IGMM, University of Edinburgh, Edinburgh, UK.
100
A collaboration between the University Medical Schools and National Health Service (NHS) in Aberdeen, Dundee, Edinburgh and Glasgow, UK.
101
Medical Research Institute, University of Dundee, Dundee, UK.
102
National Institute for Health and Welfare (THL), Helsinki, Finland.
103
Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, UK.
104
Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
105
Department of Epidemiology, Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
106
1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [2] Institute of Health Sciences, University of Oulu, Oulu, Finland. [3] Biocenter Oulu, University of Oulu, Oulu, Finland. [4] Unit of Primary Care, Oulu University Hospital, Oulu, Finland. [5] Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
107
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
108
1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Health Care Inspectorate, The Hague, the Netherlands. [3] Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. [4] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
109
Department for Genetics and Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
110
Institute of Environmental Medicine, Karolinska Institutet and Sachs' Children's Hospital, Stockholm, Sweden.
111
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
112
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
113
1] Institute of Health and Environment, Seoul National University, Seoul, South Korea. [2] Complex Disease and Genetic Epidemiology Branch, Department of Epidemiology, Seoul National University School of Public Health, Seoul, South Korea.
114
Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
115
1] Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA. [2] Department of Public Health, Division of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, New York, USA.
116
1] University of New Mexico Health Sciences Center School of Medicine, Albuquerque, New Mexico, USA. [2].
117
1] Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, UK. [2].
118
1] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA. [3].
119
1] Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, UK. [2].
120
1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Erasmus MC, Rotterdam, the Netherlands. [4].
121
1] Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA. [2].

Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

PMID:
24929828
PMCID:
PMC4140093
DOI:
10.1038/ng.3011
[Indexed for MEDLINE]
Free PMC Article

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