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 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. phs000296 ESP LungGO COPDGene phs000765 COPDGene_Geno ]]>
6-Minute Walk TestNon-COPDGene Scans Only: CT Acquisition ParametersCT Assessment ScoresheetDemographics and Physical CharacteristicsDiscontinuationEligibility FormInformed Consent and Permissions GrantedMedical HistoryMedication HistoryRespiratory Disease QuestionnaireSafety AssessmentSF-36 Health SurveySpirometrySt. George's Respiratory QuestionnaireCOPDGene CT ProtocolCT Imaging in COPDGeneGenome-wide association meta-analysis; in addition to the COPDGene study, including ARIC - Atherosclerosis Risk in Communities Study, British 1958 Birth Cohort, Cardiovascular Health Study (European ancestry), COPACETIC - COPD Pathology: Addressing Critical gaps, Early Treatment, and Innovative Conceps, ECLIPSE - Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, Lung Expression Quantitative Trait Loci Study, Framingham Heart Study, Lifelines, Lovelace Smoker's cohort, MESA - Multi-Ethnic Study of Atherosclerosis (European ancestry), NETT/NAS - National Emphysema Treatment Trial / Normative Aging Study, GenKOLS - Bergen, Norway COPD Cohort, Rotterdam Studys 1-3, SPIROMICS - Subpopulations and intermediate outcome measures in COPD study, Cardiovascular Health Study (African ancestry), KARE - Korean Association Resource project, MESA - Multi-Ethnic Study of Atherosclerosis African ancestry), MESA - Multi-Ethnic Study of Atherosclerosis (Hispanic ancestry), EOCOPD and ICGN - Boston Early-Onset COPD Study and International COPD Genetics Network, Transcontinental COPD Genetics Study, Korea, Transcontinental COPD Genetics Study, Poland.
Chronic obstructive pulmonary disease (COPD) affection status (binary) was the outcome of interest with case status defined using pre-bronchodilator spirometry values. Cases had forced expiratory volume in 1 second (FEV1) < 80% and FEV1 to forced vital capacity (FVC) ratio of < 0.7. Controls had FEV1 > 80% and FEV1/FVC > 0.7.
]]>Genome-wide association meta-analysis; in addition to the COPDGene study (non-Hispanic whites), including ARIC - Atherosclerosis Risk in Communities Study, British 1958 Birth Cohort,Cardiovascular Health Study (European ancestry), COPACETIC - COPD Pathology: Addressing Critical gaps, Early Treatment, and Innovative Conceps, ECLIPSE - Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, Lung Expression Quantitative Trait Loci Study, Framingham Heart Study, Lifelines, Lovelace Smoker's cohort, MESA - Multi-Ethnic Study of Atherosclerosis (European ancestry), NETT/NAS - National Emphysema Treatment Trial / Normative Aging Study, GenKOLS - Bergen, Norway COPD Cohort, Rotterdam Studys 1-3, SPIROMICS - Subpopulations and intermediate outcome measures in COPD study.
Chronic obstructive pulmonary disease (COPD) affection status (binary) was the outcome of interest with case status defined using pre-bronchodilator spirometry values. Cases had forced expiratory volume in 1 second (FEV1) < 80% and FEV1 to forced vital capacity (FVC) ratio of < 0.7. Controls had FEV1 > 80% and FEV1/FVC > 0.7.
]]>Genome-wide association meta-analysis; in addition to the COPDGene study including ARIC - Atherosclerosis Risk in Communities Study, British 1958 Birth Cohort, Cardiovascular Health Study (European ancestry),COPACETIC - COPD Pathology: Addressing Critical gaps, Early Treatment, and Innovative Conceps, ECLIPSE - Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, Lung Expression Quantitative Trait Loci Study, Framingham Heart Study, Lifelines, Lovelace Smoker's cohort, MESA - Multi-Ethnic Study of Atherosclerosis (European ancestry), NETT/NAS - National Emphysema Treatment Trial / Normative Aging Study, GenKOLS - Bergen, Norway COPD Cohort, Rotterdam Studys 1-3, SPIROMICS - Subpopulations and intermediate outcome measures in COPD study, Cardiovascular Health Study (African ancestry), KARE - Korean Association Resource project, MESA - Multi-Ethnic Study of Atherosclerosis African ancestry), MESA - Multi-Ethnic Study of Atherosclerosis (Hispanic ancestry).
Chronic obstructive pulmonary disease (COPD) affection status (binary) was the outcome of interest with case status defined using pre-bronchodilator spirometry values. Cases had forced expiratory volume in 1 second (FEV1) < 80% and FEV1 to forced vital capacity (FVC) ratio of < 0.7. Controls had FEV1 > 80% and FEV1/FVC > 0.7.
]]>Genome-wide association meta-analysis; included the COPDGene study, the UK Biobank, and the following ICGC cohorts: ARIC - Atherosclerosis Risk in Communities Study, Cardiovascular Health Study (African and European ancestries), ECLIPSE - Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, EOCOPD and ICGN - Boston Early-Onset COPD Study and International COPD Genetics Network, Lung Expression Quantitative Trait Loci Study, Framingham Heart Study, KARE - Korean Association Resource project, Transcontinental COPD Genetics Study, Korea, Lifelines, Lovelace, MESA - Multi-Ethnic Study of Atherosclerosis (African, European, and Hispanic ancestries), NETT/NAS - National Emphysema Treatment Trial / Normative Aging Study, GenKOLS - Bergen, Norway COPD Cohort, Transcontinental COPD Genetics Study, Poland, Rotterdam Study (1, 2 and 3), and SPIROMICS - Subpopulations and intermediate outcome measures in COPD study.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 Participation in the ECLIPSE study, Boston Early-Onset COPD Study, or International COPD Genetics Network (Selected replication cohorts) 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 Participation in the ECLIPSE study, Boston Early-Onset COPD Study, or International COPD Genetics Network (Selected replication cohorts) ]]>
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.]]>