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Lung function is an important marker of overall health. Poor lung function is associated with respiratory disability, poor quality of life and overall mortality. Individuals that experience an excessive decline in lung function with ageing, develop clinical symptoms of respiratory disability, impaired ventilatory function and, ultimately, chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. This proposal aims to improve our knowledge of the genetic, environmental and lifestyle determinants of lung function and to further understand what drives its decline with age. The proposed research will contribute to further the understanding of the factors associated with lung function and to improve the prediction of lung function decline with ageing. It fits UK Biobank?s stated purpose as it will help elucidate pathophysiological mechanisms of lung disease and contribute to the prevention, risk stratification and treatment of diseases such as COPD. Our goal is to use the UK Biobank data to assess genetic and environmental risk factors associated with lung function. We will: 1) apply new statistical approaches to the analysis of genetic data in order to find novel variants associated with lung function; 2) perform association studies of genes in candidate pathways and gene-environment interactions that influence lung function; and 3) perform Mendelian randomization studies to investigate causal effects of modifiable risk factors for lung function and lung disease (e.g. asthma and COPD), using genes as instrumental variables. We request access to the entire cohort, including follow-ups, and to all currently available genotype data. The data from the entire cohort will be used for the purpose of conducting epidemiological analyses investigating genetic and non-genetic factors associated with lung function and disease.