Genome-wide association analyses in COPD to date have included subjects with mild or moderately severe airflow limitation7,9,12,22. To our knowledge, a genome-wide association case-control study of severe COPD has not been previously reported. The severity of airflow limitation in COPD correlates with many other important disease characteristics, such as emphysema23, functional limitation24, and higher mortality25. In addition to potentially identifying novel signals unique to severe disease, a genome-wide association study of severe COPD may have improved power compared with a study of moderate-to-severe COPD due to decreased phenotypic heterogeneity and misclassification in severe COPD cases, as well as enrichment for subjects with the highest genetic risk profile26–30, despite the decreased sample size.
