10,000 subjects are planned to be enrolled with 2/3 non-Hispanic White and 1/3 African American, distributed across the full spectrum of disease severity and both genders. The cohort is specifically being recruited for a genome-wide association study (GWAS) analysis and is large enough to provide adequate statistical power to detect genetic variants exerting modest effects on risk. COPD subtypes will be defined based on the presence and severity of parenchymal and airway disease on inspiratory and expiratory high-resolution chest CT scans. The Genome-Wide Association Study (GWAS) was designed to involve four phases. There will be an initial GWAS on a balanced group of 4000 subjects of current or former smoker case and control subjects (2600 White and 1400 African American) in Phase 1. Statistical signals (SNPs in or between genes) identified in Phase I will be confirmed in Phase II with a custom SNP array using the remaining 2000 cases and 2000 controls in the cohort. In Phase III SNPs in genes/regions identified and confirmed in Phases I and II will be investigated with regional fine mapping and tests of associations to identify causal genes. The final group of candidate genes will be replicated in other COPD cohorts as Phase IV. With continued improvements in SNP genotyping technology additional phases (beyond Phase 1) may be analyzed at the genome-wide level.
The COPDGene cohort is also established for longitudinal follow-up with regular contacts made to determine mortality, comorbid disease events and disease status. Renewed funding will be sought to re-assess the subjects with spirometry, clinical evaluation and repeat chest CT to accumulate information about progression of the disease.