Genetic Epidemiology of COPD (COPDGene) Funded by the National Heart, Lung, and Blood Institute

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 will establish a racially diverse cohort that is sufficiently large and appropriately designed for genome-wide association analysis of COPD. A total of 10,000 subjects will be recruited, including control smokers, definite COPD cases (GOLD Stage 2 to 4), and subjects not included in either group (GOLD 1 or GOLD-Unclassified). This cohort will be used for cross-sectional analysis, although long-term longitudinal follow-up will be a future goal. The primary focus of the study will be genome-wide association analysis 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 initial phase of genome-wide association analysis included 500 COPD cases and 500 control subjects (all non-Hispanic White) genotyped with the Illumina Omni-1 chip. The second phase genotyped the entire study cohort using the Illumina Omni-Express chip. Unique aspects of the study include: 1) Inclusion of large numbers of African American subjects (approximately 1/3 of the cohort); 2) Obtaining chest CT scans (including inspiratory and expiratory images); and 3) Inclusion of the full range of disease severity.

The COPDGene_v6 Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" section of this top-level study page phs000179 COPDGene_v6 Cohort.

• phs000296 ESP LungGO COPDGene
• phs000765 COPDGene_Geno

• Study Weblinks:
  • COPDGene
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 10371
• Subject Sample Telemetry Report (SSTR)

• BioProject
• Sequence Read Archive
• BioSample
• MeSH

COPD Cases:

Inclusion Criteria
Age 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

Smokers without COPD:

Inclusion Criteria
Age 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)
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

This 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.

• Primary Phenotype: Pulmonary Disease, Chronic Obstructive
• Emphysema

• Principal Investigators
  • James D. Crapo. National Jewish Health, Denver, CO, USA.
  • Edwin K. Silverman. Brigham and Women's Hospital, Boston, MA, USA.
• Institute
  • National Heart, Lung and Blood Institute, Bethesda, MD, USA.
• Funding Source
  • U01HL089897. National Institutes of Health, Bethesda, MD, USA.
  • U01HL089856. National Institutes of Health, Bethesda, MD, USA.