Study of common and rare genetic variants in respiratory health: the UK Biobank Lung Exome Evaluation (UK BiLEVE) consoertium

Nine hundred thousand people in the UK have COPD, a progressive lung disease that blocks airways, yet not all smokers develop it—genetics holds the key to why. The problem is that current treatments for COPD are blunt instruments. Smoking is the main risk factor, but inherited differences in lung function make some people far more vulnerable than others. Researchers have already found common genetic variants linked to lung health, but these explain only a small fraction of the risk. Rare genetic variants, which often have much larger effects on disease, remain largely undiscovered because they require very large studies to detect. This project will search for those rare variants by analysing DNA from 50,000 UK Biobank participants, using a custom respiratory exome chip that targets protein-coding genes. Participants were selected based on their smoking history and lung function, creating a powerful dataset to link specific genetic changes to airway obstruction. If successful, the findings could reveal new molecular targets for drug development—proteins or pathways that current treatments do not touch. They could also enable stratified medicine, where patients are grouped by genetic risk and given treatments tailored to their underlying biology. This is fundamental science with a clear translational path: understanding why some lungs stay healthy despite heavy smoking could lead to therapies that protect the lungs of everyone.