Multi-ancestry Genome-Wide Association Study and Meta-Analysis of Lung Function Decline

Despite evidence for a genetic component, few genetic associations with lung function decline have been identified. We aimed to evaluate genome-wide associations and putative downstream functionality of genetic variants for lung function decline. We conducted genome-wide association study (GWAS) analyses of decline in FEV1, FVC, and FEV1/FVC in 52,056 White (N = 44,988), Black (N = 5,788), Hispanic (N = 550), and Chinese American (N = 730) participants across seven general population cohorts. GWAS analyses were stratified by cohort, ancestry, and sex. Results were combined in cross-ancestry and ancestry-specific meta-analyses. Significant variants available in two independent COPD-enriched cohorts were tested for replication. We identified 361 distinct genome-wide significant (p < 5E-08) variants for one or more of the FEV1, FVC, and FEV1/FVC decline phenotypes, which overlapped with previously reported genetic signals for pulmonary traits. Four variants, or 10.3