Large-scale genomic epidemiology approaches to study the natural history of lung function and COPD (360G-Wellcome-202849_Z_16_Z)

Whilst risk factors for COPD are known, the determinants of lung function, COPD susceptibility and progression of COPD are incompletely understood. More effective approaches to prevention and treatment are urgently needed. We discovered genomic variants at many independent loci associated with lung function and risk of COPD. We and others have developed genomic epidemiology resources of unprecedented size utilising genome-wide genotyping arrays. Combined with genome-wide imputation, new statistical genetic approaches and epidemiological studies with measured lung function and electronic medical records we will advance understanding of the associations known to date and generate novel discoveries. We will fine-map loci to inform functional studies and study pleiotropic effects of associated variants. Using risk scores of variants showing genome-wide association and also genome-wide polygenic risk scores, we will assess the potential for improved prediction of COPD. We will develop methods to make more complete use of electronic medical record data and apply these in UK Biobank to boost the power to study disease relevant phenotypes. We will harness UK Biobank and large consortia to facilitate subgroup analyses at scale to generate novel insights into clinical heterogeneity in the natural history of lung function, COPD susceptibility and progression of COPD.