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Study Description

This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying document, "TOPMed Whole Genome Sequencing Project". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

This study contains whole genome sequence data and harmonized phenotype variables produced as part of NHLBI's Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing (WGS) project.

The National Heart, Lung and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program is designed to generate scientific resources to enhance understanding of fundamental biological processes that underlie heart, lung, blood and sleep disorders (HLBS). It is part of a broader Precision Medicine Initiative which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so this program seeks to uncover factors that increase or decrease the risk of disease, identify subtypes of disease, and develop more targeted and personalized treatments. The Whole Genome Sequencing (WGS) project is part of NHLBI's TOPMed program and serves as an initial step for the larger initiative.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and the only leading cause of death that is steadily increasing in frequency. This project established a racially diverse cohort that is sufficiently large and appropriately designed for genome-wide association analysis of COPD. A total of 10,720 subjects were recruited, including control smokers and nonsmokers, definite COPD cases (GOLD Stage 2 to 4), and subjects not included in either group (GOLD 1 and PRISm). This cohort is being used for cross-sectional analysis, and long-term longitudinal follow-up visits after five years and after ten years are also being performed. The primary focus of the study is to identify the genetic risk factors that determine susceptibility for COPD and COPD-related phenotypes. Detailed phenotyping of both cases and controls, including chest CT scan assessment of emphysema and airway disease, will allow identification of genetic determinants for the heterogeneous components of the COPD syndrome. The hypotheses to be studied are: 1) Precise phenotypic characterization of COPD subjects using computed tomography, as well as clinical and physiological measures, will provide data that will enable the broad COPD syndrome to be decomposed into clinically significant subtypes. 2) Genome-wide association studies will identify genetic determinants for COPD susceptibility that will provide insight into clinically relevant COPD subtypes. 3) Distinct genetic determinants influence the development of emphysema and airway disease. The TOPMed analysis will include approximately 10,500 subjects with whole genome sequencing after quality control is completed.

Comprehensive phenotypic data for COPDGene subjects is available through dbGaP entry phs179.v5.p2.

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

COPD Cases:
Inclusion Criteria
Age at Enrollment: 45 - 80 years
Smoking history of ≥ 10 pack-years
Diagnosis of COPD Stages 2, 3 and 4 by GOLD criteria (post-bronchodilator FEV1/FVC < 0.70 and FEV1 < 80% predicted)
Non-Hispanic White or non-Hispanic African American
Exclusion Criteria
Concomitant respiratory disorder other than asthma or COPD (such as, but not limited to, diffuse bronchiectasis, cystic fibrosis, or interstitial lung disease)
Lung surgery with removal of a lobe or more (including lung volume reduction surgery or lung transplantation)
Lung cancer, known or suspected
Surgical or bronchoscopic lung volume reduction
Pregnancy or suspected pregnancy
Uncontrolled cancer, defined as ongoing radiation therapy, ongoing chemotherapy, narcotics for pain control, or known metastatic disease
History of radiation therapy to the chest (other than for breast cancer)
Use of antibiotics and/or systemic steroids (new prescription or increased dose) for a COPD exacerbation or respiratory infection within the last month
Inability to use albuterol
First or second degree relative (parent, brother, sister, daughter, son, aunt, uncle, nephew, niece, half-sibling, grandparent, grandchild) of a subject enrolled in COPDGene
Subjects who indicate they are in more than one racial category
Metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, or metal shoulder prosthesis
Subjects with affirmative answers to the following:

  • chest or abdominal surgery in the past three months
  • a heart attack in the last three months
  • detached retina or eye surgery in the past three months
  • hospitalization for any other heart problem in the past month

Participation in the ECLIPSE study, Boston Early-Onset COPD Study, or International COPD Genetics Network (Selected replication cohorts)

Smokers without COPD
Inclusion Criteria
Age at Enrollment: 45 - 80 years
History (current or formerly) of cigarette smoking ≥ 10 pack-years
Post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 ≥ 80% predicted
Non-Hispanic White or non-Hispanic African American
Exclusion Criteria
Physician diagnosed respiratory disease other than COPD or asthma (based on subject report)
Lung surgery with removal of a lobe or more (including lung volume reduction surgery and lung transplantation)
Pregnancy or suspected pregnancy
Lung cancer, known or suspected
Uncontrolled cancer, defined as ongoing radiation therapy, ongoing chemotherapy, narcotics for pain control, or known metastatic disease
History of radiation therapy to the chest
Use of antibiotics (new prescription or increased dose) for a respiratory infection within the past month
Use of systemic corticosteroids (new prescription or increased dose) for a respiratory process within the past month
Inability to use albuterol
First or second degree relative (parent, brother, sister, daughter, son, aunt, uncle, nephew, niece, half-sibling, grandparent, or grandchild) of a subject enrolled in COPDGene
Subjects who indicate they are in more than one racial category
Metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, or metal shoulder prosthesis
Subjects with affirmative answers to the following:

  • chest or abdominal surgery in the past three months
  • a heart attack in the last three months
  • detached retina or eye surgery in the past three months
  • hospitalization for any other heart problem in the past month

Participation in the ECLIPSE study, Boston Early-Onset COPD Study, or International COPD Genetics Network (Selected replication cohorts)

Note that similar enrollment criteria were utilized for lifelong nonsmoking control subjects.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Sequencing Illumina HiSeq X Ten N/A N/A
Study History

The COPDGene Study was funded by the NHLBI in October 2007 as two U01 grants-one to National Jewish Medical and Research Center (PI: James D. Crapo) and one to Brigham and Women's Hospital (PI: Edwin K. Silverman). After a pilot study in 2007, study recruitment began in February 2008 at 21 clinical centers throughout the United States. In 2012, the NHLBI funded longitudinal assessment of the COPDGene cohort and additional genetic analysis through paired R01 grants. In 2017, the COPDGene project was refunded as two U01 grants to support further longitudinal follow-up.

Selected publications
Diseases/Traits Related to Study (MESH terms)
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Study Attribution