Study Design

Initial COPDGene® Study Design


Background: COPDGene is a multicenter observational study designed to identify genetic factors associated with COPD. It will also characterize chest CT phenotypes in COPD subjects, including assessment of emphysema, gas trapping, and airway wall thickening. Finally, subtypes of COPD based on these phenotypes will be used in a comprehensive genome-wide study to identify COPD susceptibility genes.

Methods/Results: COPDGene has enrolled more than 10,000 smokers with and without COPD across the GOLD stages. Both Non-Hispanic white and African-American subjects are included in the cohort. Inspiratory and expiratory chest CT scans have been obtained on all participants. In addition to the cross-sectional enrollment process, these subjects are being followed regularly with questionnaires for longitudinal studies. A genome-wide association study (GWAS) is being performed on all COPDGene subjects to identify common genetic variants associated with COPD and COPD-related phenotypes.

Conclusions: COPDGene will provide important new information about genetic factors in COPD, and will characterize the disease process using high resolution CT scans. Understanding genetic factors and CT phenotypes that define COPD will potentially permit earlier diagnosis of this disease and may lead to the development of treatments to modify progression.


Details of the initial study design have been published.  To read the article, as published in COPD: The Journal of Chronic Obstructive Lung Disease, click here.


Revised COPDGene® Study Design  

COPDGene is a cross sectional prospective cohort enrolled between January 2008 and June 2011 at 21 Clinical Centers.  The study goals were to characterize smokers with and without COPD, using spirometry, six minute walk, medical history, respiratory symptoms (modified ATS respiratory questionnaire), respiratory medications, quality of life and inspiratory and expiratory chest CT scans, and to perform epidemiological and genetic studies of these COPD-related phenotypes.


The original study design for COPDGene® included three groups of subjects, with plans for 4500 smoker controls and 1500 GOLD 1 subjects and 4500 subjects in GOLD Stages 2-4 (1500 for each of the three GOLD stages) for a total of 10,500.  Non-Hispanic Whites were planned to be 2/3 of each group and Non-Hispanic African Americans 1/3 of each group.  All subjects had at least 10 pack-years of smoking.

Changes to the final enrollment groups:

1. Smoker Controls: Normal spirometry (FEV1/FVC ratio >0.7, FEV1> 80% predicted) goal of 4000 subjects

2. COPD "At Risk" Groups (GOLD 1 and GOLD-U): We decided to include GOLD-Unclassified subjects (for a description of this group see (Wan ES, et al. Am J Respir Crit Care Med 2011;Jul 1;184(1):57-63)), and add them to the total planned for GOLD 1. These groups together had a final goal of 2000 subjects.

3. GOLD 2-4, COPD Cases: The enrollment goal for this group remains at the planned 4000 subjects

4. Non Smokers: Initial reviews of the smoker control group demonstrated CT evidence of disease and a small (100) group of similar aged non-smokers were enrolled to provide a comparison point for CT scans in the aging lung.

5. Total enrollment for the study reduced to 10,000 plus non-smoker controls, no change in racial group proportions

Genotyping Strategy

1. Original Study Design (Note: NHW and AA totals are combined for simplicity, but include 2/3 NHW and 1/3 African Americans at each Phase)

a. Phase 1 (Genome-wide): 1500 Cases vs. 1500 Controls with genome-wide chip

b. Phase 2 (Replication): 1500 Cases vs. 1500 Controls for 6144 SNPs

c. Phase 3 (Fine Mapping): 1500 Cases vs. 1500 Controls for 1536 SNPs

d. Phase 4 (All Subjects):

i. Fast Track Panel: 3000 Cases vs. 3000 Controls (Phase 1 and 2 subjects) for 1536 SNPs

ii. 4500 Cases vs. 4500 Controls (COPDGene®), 3100 International COPD Genetics Network (ICGN), 1500 GOLD 1, and 1100 Boston Early-Onset COPD Study (EOCOPD) for 768 SNPs

2. Revised Genotyping

a. Whole genome genotyping of the full COPDGene cohort with the Illumina Omni-Express Chip.

b. Replication Genotyping: ICGN and EOCOPD Studies will be genotyped for significantly associated SNPs from the COPDGene GWAS.

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