Chronic obstructive pulmonary disease (COPD), characterized by persistent and usually progressive airflow obstruction, is one of the leading causes of morbidity and mortality worldwide. While cigarette smoking is the major environmental risk factor, the burden of COPD is increasing1,2 despite many successful efforts at tobacco control, and the response to cigarette smoke is characterized by high inter-individual variability3. Genetic factors are a major contributor to this variability4–6, but the specific genetic loci responsible for this variation remain largely unknown7. Genome-wide association studies have successfully identified loci which are often novel for a range of complex diseases, including COPD, that have subsequently replicated8–17, but the majority of genetic susceptibility due to common variation remains unexplained18. Identifying genetic loci may lead to improved risk prediction and subtype identification19, and is arguably the most promising unbiased approach to understand disease mechanisms in humans and enable future specific and rational therapies20.
