Genetic epidemiology of COPD (COPDGene) study design

Elizabeth A Regan, John E Hokanson, James R Murphy, Barry Make, David A Lynch, Terri H Beaty, Douglas Curran-Everett, Edwin K Silverman, James D Crapo, Elizabeth A Regan, John E Hokanson, James R Murphy, Barry Make, David A Lynch, Terri H Beaty, Douglas Curran-Everett, Edwin K Silverman, James D Crapo

Abstract

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 will enroll 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 will be obtained on all participants. In addition to the cross-sectional enrollment process, these subjects will be followed regularly for longitudinal studies. A genome-wide association study (GWAS) will be done on an initial group of 4000 subjects to identify genetic variants associated with case-control status and several quantitative phenotypes related to COPD. The initial findings will be verified in an additional 2000 COPD cases and 2000 smoking control subjects, and further validation association studies will be carried out.

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.

Conflict of interest statement

Dr Regan has no conflicts to disclose, Dr Hokanson has no conflicts to disclose, Dr Murphy has no conflicts to disclose, Dr Make has no conflicts to disclose, Dr Lynch has received consulting fees from Intermune, Gilead, Centocor, and Novartis; he is a member of the advisory board for the BUILD-3 study sponsored by Actelion. Dr Beaty has no conflicts to disclose. Dr Curran-Everett has no conflicts to disclose. Dr Silverman has received grant funding from Glaxo Smith Kline, consulting fees from Astra Zeneca and Glaxo Smith Kline and honoraria from Bayer, Glaxo Smith Kline and Astra Zeneca, Dr Crapo has no conflicts to disclose.

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