Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Brian D
http://orcid.org/0000-0001-9564-0745
BD
Hobbs
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
Kim
K
de Jong
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada.
Maxime
M
Lamontagne
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada.|Department of Molecular Medicine, Laval University, Québec, Québec, Canada.
Yohan
http://orcid.org/0000-0002-3067-3711
Y
Bossé
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
Nick
N
Shrine
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
María Soler
MS
Artigas
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
Louise V
http://orcid.org/0000-0003-4951-1867
LV
Wain
Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Ian P
IP
Hall
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
Victoria E
VE
Jackson
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.
Annah B
AB
Wyss
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.
Stephanie J
http://orcid.org/0000-0003-4911-5290
SJ
London
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Kari E
KE
North
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Nora
N
Franceschini
Population Health Research Institute, St George's, University of London, London, UK.
David P
http://orcid.org/0000-0001-7854-1366
DP
Strachan
Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Terri H
TH
Beaty
Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
John E
JE
Hokanson
Department of Medicine, Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colorado, USA.
James D
JD
Crapo
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of General Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Peter J
PJ
Castaldi
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Robert P
RP
Chase
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.|Department of Biostatistics, University of Washington, Seattle, Washington, USA.
Traci M
TM
Bartz
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.|Department of Epidemiology, University of Washington, Seattle, Washington, USA.|Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
Susan R
SR
Heckbert
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.|Department of Epidemiology, University of Washington, Seattle, Washington, USA.|Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.|Department of Health Services, University of Washington, Seattle, Washington, USA.
Bruce M
BM
Psaty
Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
Sina A
SA
Gharib
Department of Pulmonology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
Pieter
P
Zanen
Department of Pulmonology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
Jan W
JW
Lammers
University of Groningen, University Medical Center Groningen, Center for Medical Imaging, Groningen, the Netherlands.
Matthijs
M
Oudkerk
University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands.
H J
HJ
Groen
GSK R&D, King of Prussia, Pennsylvania, USA.
Nicholas
N
Locantore
GSK R&D, King of Prussia, Pennsylvania, USA.
Ruth
R
Tal-Singer
Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Clinical Discovery Unit, AstraZeneca, Cambridge, UK.
Stephen I
SI
Rennard
School of Biological Sciences, University of Manchester, Manchester, UK.
Jørgen
J
Vestbo
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands.
Wim
http://orcid.org/0000-0002-4146-6363
W
Timens
University of British Columbia Center for Heart Lung Innovation and Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada.
Peter D
PD
Paré
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Jeanne C
JC
Latourelle
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.|National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
Josée
J
Dupuis
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.|Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
George T
GT
O'Connor
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
Jemma B
JB
Wilk
Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
Woo Jin
WJ
Kim
Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
Mi Kyeong
MK
Lee
Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Yeon-Mok
YM
Oh
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
Judith M
JM
Vonk
Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Harry J
HJ
de Koning
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Shuguang
S
Leng
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Steven A
SA
Belinsky
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Yohannes
Y
Tesfaigzi
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.|Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
Ani
A
Manichaikul
Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
Xin-Qun
XQ
Wang
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.|Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
Stephen S
SS
Rich
Department of Medicine, College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
R Graham
RG
Barr
VA Boston Healthcare System and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
David
D
Sparrow
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Augusto A
AA
Litonjua
Department of Clinical Science, University of Bergen, Bergen, Norway.
Per
P
Bakke
Department of Clinical Science, University of Bergen, Bergen, Norway.
Amund
A
Gulsvik
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Lies
http://orcid.org/0000-0002-3494-4363
L
Lahousse
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.|Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Guy G
GG
Brusselle
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Netherlands Health Care Inspectorate, The Hague, the Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.|Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, the Netherlands.
Bruno H
BH
Stricker
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.|Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, the Netherlands.
André G
AG
Uitterlinden
Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Elizabeth J
EJ
Ampleford
Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Eugene R
ER
Bleecker
Cardiovascular Research Institute and Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of California at San Francisco, San Francisco, California, USA.
Prescott G
PG
Woodruff
Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Deborah A
DA
Meyers
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Dandi
D
Qiao
University College London, London, UK.
David A
DA
Lomas
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jae-Joon
JJ
Yim
Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.
Deog Kyeom
DK
Kim
2nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
Iwona
I
Hawrylkiewicz
2nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
Pawel
P
Sliwinski
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Clinical Discovery Unit, AstraZeneca, Cambridge, UK.
Megan
M
Hardin
Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado, USA.|Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, Colorado, USA.
Tasha E
TE
Fingerlin
Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado, USA.|Department of Medicine, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.|Department of Immunology, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
David A
DA
Schwartz
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands.
Dirkje S
DS
Postma
University of Edinburgh, Edinburgh, UK.
William
W
MacNee
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.|National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Martin D
http://orcid.org/0000-0002-3596-7874
MD
Tobin
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Edwin K
EK
Silverman
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
H Marike
HM
Boezen
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Michael H
http://orcid.org/0000-0002-4907-1657
MH
Cho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001249:Asthma / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008168:Lung / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics