Pulmonary function is an easily measurable and reliable index of the physiological state of the lungs and airways1. Pulmonary function also predicts mortality in the general population, even among never smokers with only modestly reduced pulmonary function and without respiratory symptoms2,3. The peak level of pulmonary function attained in early adulthood and its subsequent decline with age are likely influenced by genetic and environmental factors. Tobacco smoking is a major environmental cause of accelerated decline in pulmonary function with age. Other inhaled pollutants also appear to contribute. Familial aggregation studies suggest a genetic contribution to lung function with heritability estimates exceeding 40%4,5, but little is known about specific genetic factors involved. A relatively uncommon deficiency of α1-antitrypsin is the only established genetic risk factor for accelerated decline in pulmonary function and development of chronic obstructive pulmonary disease (COPD), especially in smokers4,6. However, α1-antitrypsin accounts for little of the population variability in pulmonary function4. Candidate gene studies suggest that other genetic variants may influence the time course of pulmonary function and its decline in relation to smoking, but these putative genetic risk factors remain unknown4.
