Genetic epidemiology of lung function and chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Lung function measures obtained through spirometry play a key role in the diagnosis of COPD. Both COPD and lung function are affected by genetic factors, and identifying genetic variants that have an effect on lung function or COPD risk has the potential to lead to improved treatment and prevention of COPD. This thesis is structured in five chapters, an introductory, a concluding chapter and three main chapters which present different approaches that aim to bring insights into the genetics of COPD and lung function. Chapter 2 tests the association with COPD risk of genetic variants previously associated with lung function, and tests their combined effect on lung function and COPD risk, in order to explore the role of risk prediction. Chapter 3 aims to identify new genetic variants associated with lung function and tests the association of genetic variants genome-wide. Chapter 4 focuses on the analysis of low frequency variants using different approaches and methodologies, and includes two studies. One study assesses associations of low frequency variants genome-wide, and the other focuses on genetic regions associated with lung function, in order to improve the localization of association signals that often comprise broad regions and several genes. These studies overall have identified 16 new genetic variants associated with lung function, have shown the association with COPD of 4 genetic variants previously associated with lung function, and present suggestive evidence of association with COPD for low frequency variants within regions associated with lung function.