Common and rare genetic variants in respiratory health: the UK Biobank Lung Exome Variant Evaluation (UK BiLEVE) consortium

Lung function is an important indicator of respiratory health and mortality. Measures of lung function show irreversible airway obstruction in chronic obstructive pulmonary disease (COPD), a progressive condition affecting 900,000 people in the UK. Smoking is a strong risk factor for COPD but not all smokers are equally susceptible. Genetic approaches to understanding the mechanisms underlying the maintenance of good lung function in some people, and underlying the development of COPD in others, aim to reveal previously unknown molecular targets for drug development and to facilitate stratified approaches to treatment and care. This project aims to detect rare genetic variants associated with lung function. Once discovered, such variants would be very useful tools for the scientific community, because such variants tend to exert a large effect on disease risk and provide a means to translate findings from genetic studies of lung function to clinical relevant research and development. The proposed study leverages the power of UK Biobank and the resources and experience of an expert group of UK collaborators in respiratory genomics to advance understanding of lung function and COPD. This project will use a customised respiratory exome chip in 50,000 UK Biobank participants, selected according to their smoking history and lung function status at baseline. This project therefore requires the use of data (spirometry, smoking and other lifestyle factors) and DNA samples.