Genetic Epidemiology of COPD (COPDGene) Study Design

TLDR

COPDGene is a multicenter observational study designed to identify genetic factors associated with COPD. The study aims to characterize chest CT phenotypes in COPD subjects and use these phenotypes to define COPD subtypes for a genome‑wide association study to identify susceptibility genes. The study enrolls 10,000 smokers across GOLD stages, includes Non‑Hispanic white and African‑American subjects, obtains inspiratory and expiratory chest CT scans, follows participants longitudinally, and performs a GWAS on an initial 4,000 subjects to identify variants linked to case‑control status and quantitative phenotypes. Initial GWAS results were validated in additional cases and controls, revealing genetic variants linked to COPD and CT phenotypes that could enable earlier diagnosis and inform therapeutic development.

Abstract

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.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.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.