Evidence map›Paper›PMID 24621683›Full record

SynthesisThe Lancet. Respiratory medicine2014

Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis.

Michael H Cho, Merry-Lynn N McDonald, Xiaobo Zhou, Manuel Mattheisen, Peter J Castaldi, Craig P Hersh, Dawn L Demeo, Jody S Sylvia, John Ziniti, Nan M Laird and 20 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Respiratory medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
227citing papers in PubMed, 7 pooled it
27.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

227 citing papers in PubMed, 7 syntheses or guidelines pooled it, 360 citations in OpenAlex.

  1. Pooled it
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  8. International journal of molecular sciences · 2025
    Trial
  9. Trial
  10. Genome-Wide Association Analysis of Single-Breath DlAmerican journal of respiratory cell and molecular biology · 2019
    Trial
  11. Trial
  12. Trial
  13. Trial
  14. Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis.American journal of respiratory cell and molecular biology · 2017
    Trial
  15. Article
  16. Review
  17. Article
  18. HHIP's dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  19. Long isoforms of the COPD risk gene FAM13A orchestrate human lung epithelial development.American journal of respiratory cell and molecular biology · 2026
    Article
  20. Article

167 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 12 institutions in 3 countries.

Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: remhc@channing.harvard.edu.
Merry-Lynn N McDonaldChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Xiaobo ZhouChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Manuel MattheisenChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard School of Public Health, Boston, MA, USA.
Peter J CastaldiChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Craig P HershChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Dawn L DemeoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Jody S SylviaChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
John ZinitiChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Nan M LairdHarvard School of Public Health, Boston, MA, USA.
Christoph LangeHarvard School of Public Health, Boston, MA, USA.
Augusto A LitonjuaChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
David SparrowSchool of Public Health and School of Medicine, Boston University, Boston, MA, USA; Veterans Administration Boston Healthcare System, Boston, MA, USA.
Richard CasaburiLos Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA, USA.
R Graham BarrDepartment of Medicine, College of Physicians and Surgeons, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Elizabeth A ReganNational Jewish Health, Denver, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA.
Barry J MakeNational Jewish Health, Denver, CO, USA.
John E HokansonDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA.
Sharon LutzDepartment of Bioinformatics and Statistics, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA.
Tanda Murray DudenkovJohns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Homayoon FarzadeganJohns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Jacqueline B HetmanskiJohns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Ruth Tal-SingerGlaxoSmithKline Research and Development, King Of Prussia, PA, USA.
David A LomasUniversity College London, London, UK.
Per BakkeDepartment of Clinical Science, University of Bergen, Bergen, Norway; Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
Amund GulsvikDepartment of Clinical Science, University of Bergen, Bergen, Norway; Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
James D CrapoNational Jewish Health, Denver, CO, USA.
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Terri H BeatyJohns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
NETT Genetics, ICGN, ECLIPSE and COPDGene Investigators
Brigham and Women's Hospital · USJohns Hopkins University · USHarvard University · USUniversity of Colorado Denver · USUniversity of Bergen · NOColorado School of Public Health · USColumbia University · USGlaxoSmithKline (United States) · USHarbor–UCLA Medical Center · USNational Jewish Health · USUniversity College London · GBVA Boston Healthcare System · US

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Genetic Epidemiology of COPDU01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2007 to 2021
$56.9M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Metabolomic signatures of empysema and COPD progression in the COPDGene cohortR01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2012 to 2016
$31.1M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
(2 of 2) Genetic Epidemiology of COPDR01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2012 to 2016
$18.9M
Systems Biology, Bioinformatics, and BiostatisticsP01HL105339 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2011 to 2015
$12.2M
Statistical GeneticsP01HL083069 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2007 to 2011
$12.2M
GRADUATE TRAINING IN BIOSTATISTICST32ES007142 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI Brent Andrew Coull · 1985 to 2026
$11.9M
Identifying Genetic Determinants of Severe, Early-Onset COPDR01HL113264 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHO, MICHAEL H., SILVERMAN, EDWIN K · 2012 to 2016
$6.0M
Genetic Determinants of COPD in Diverse Ethnic GroupsR01HL084323 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2010
$2.6M
Impact of CPAP on Functional Outcomes in Milder OSAR01HL076101 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI WEAVER, TERRI ELIZABETH · 2003 to 2006
$2.6M
Medical Research Council G0901786NCATS NIH HHS UL1 TR000005NCATS NIH HHS UL1 TR001079NHLBI NIH HHS K08 HL097029NHLBI NIH HHS N01 HR076101NHLBI NIH HHS N01 HR076102NHLBI NIH HHS N01 HR076103NHLBI NIH HHS N01 HR076104NHLBI NIH HHS N01 HR076105NHLBI NIH HHS N01 HR076106NHLBI NIH HHS N01 HR076107NHLBI NIH HHS N01 HR076108NHLBI NIH HHS N01 HR076109NHLBI NIH HHS N01 HR076110NHLBI NIH HHS N01 HR076111NHLBI NIH HHS N01 HR076112NHLBI NIH HHS N01 HR076113NHLBI NIH HHS N01 HR076114NHLBI NIH HHS N01 HR076115NHLBI NIH HHS N01 HR076116NHLBI NIH HHS N01 HR076118NHLBI NIH HHS N01 HR076119NHLBI NIH HHS N01HR76117NHLBI NIH HHS P01 HL083069NHLBI NIH HHS P01 HL105339NHLBI NIH HHS R01 HL084323NHLBI NIH HHS R01 HL089856NHLBI NIH HHS R01 HL089897NHLBI NIH HHS R01 HL113264NHLBI NIH HHS U01 HL089856NHLBI NIH HHS U01 HL089897NIEHS NIH HHS R25 ES011080NIEHS NIH HHS T32 ES007142
6 · The paper itself

Abstract

backgroundThe genetic risk factors for susceptibility to chronic obstructive pulmonary disease (COPD) are still largely unknown. Additional genetic variants are likely to be identified by genome-wide association studies in larger cohorts or specific subgroups. We sought to identify risk loci for moderate to severe and severe COPD with data from several cohort studies.

methodsWe combined genome-wide association analysis data from participants in the COPDGene study (non-Hispanic white and African-American ethnic origin) and the ECLIPSE, NETT/NAS, and Norway GenKOLS studies (self-described white ethnic origin). We did analyses comparing control individuals with individuals with moderate to severe COPD and with a subset of individuals with severe COPD. Single nucleotide polymorphisms yielding a p value of less than 5 × 10(-7) in the meta-analysis at loci not previously described were genotyped in individuals from the family-based ICGN study. We combined results in a joint meta-analysis (threshold for significance p<5 × 10(-8)).

findingsAnalysis of 6633 individuals with moderate to severe COPD and 5704 control individuals confirmed association at three known loci: CHRNA3 (p=6·38 × 10(-14)), FAM13A (p=1·12 × 10(-14)), and HHIP (p=1·57 × 10(-12)). We also showed significant evidence of association at a novel locus near RIN3 (p=5·25 × 10(-9)). In the overall meta-analysis (ie, including data from 2859 ICGN participants), the association with RIN3 remained significant (p=5·4 × 10(-9)). 3497 individuals were included in our analysis of severe COPD. The effect estimates for the loci near HHIP and CHRNA3 were significantly stronger in severe disease than in moderate to severe disease (p<0·01). We also identified associations at two additional loci: MMP12 (overall joint meta-analysis p=2·6 × 10(-9)) and TGFB2 (overall joint meta-analysis p=8·3 × 10(-9)).

interpretationWe have confirmed associations with COPD at three known loci and identified three new genome-wide significant associations. Genetic variants other than in α-1 antitrypsin increase the risk of COPD.

fundingUS National Heart, Lung, and Blood Institute; the Alpha-1 Foundation; the COPD Foundation through contributions from AstraZeneca, Boehringer Ingelheim, Novartis, and Sepracor; GlaxoSmithKline; Centers for Medicare and Medicaid Services; Agency for Healthcare Research and Quality; and US Department of Veterans Affairs.

Indexed as

Genetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPulmonary Disease, Chronic Obstructive

Identifiers

PMID24621683
PMCPMC4176924
OpenAlexW2005623173

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.