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
