A Better Understanding of COPD and Genetics

By Jane Farrell

Researchers have uncovered 13 new genetic regions that are linked to Chronic Obstructive Pulmonary Disease (COPD). The illness is the third leading cause of death in the U.S.

Smoking still is the most important risk factor for COPD, but the discovery expands the understanding of the role genetics plays.

The finding, by researchers from Brigham and Women’s Hospital (BWH) in Boston, was published in the journal Nature Genetics. The investigators also found that the genetic risk of COPD overlaps with two other lung diseases, asthma and pulmonary fibrosis.

“We are excited about these findings because we have not only uncovered new genetic risk factors for COPD, but also shown overlap of COPD genetic risk with the risk to asthma and pulmonary fibrosis,” said lead author Brian Hobbs, MD, MMSc a physician-researcher in the Channing Division of Network Medicine and Pulmonary and Critical Care Division of BWH.

“This is the first step in a longer process in which we hope to better understand the genetic basis for COPD, or what may be several different diseases that present as COPD. Now that we know there are new regions of the genome associated with COPD, we can build on this research by probing new biological pathways with the ultimate goal of improving therapies for our patients with this disease.”

Researchers conducted a genome-wide association study of risk for chronic obstructive pulmonary disease (COPD) in a large, multi-ancestry cohort (15,256 cases and 47,936 controls).  This type of study allows investigators to look across a comprehensive set of genetic variants in different individuals to see if any variant is associated with disease. Top findings from this study were replicated in a second cohort. The authors also sought to understand more about their findings by examining overlap with other diseases and examining what was known about gene function in these regions. In addition to identifying 13 new genetic regions associated with COPD, they also discovered four genetic regions that were not previously associated with any lung function trait. Nine of the genetic regions have been identified as playing an important role in lung function. Two have previously shown an association with pulmonary fibrosis; however, the specific forms of these genetic variants that increase risk for COPD decrease risk for pulmonary fibrosis. All analyses accounted for the effects of age, gender, and cigarette smoking on disease risk.

“While it is extremely important that patients not smoke for many health reasons – including the prevention of COPD – we know that smoking cessation may not be enough to stave off the disease,” said Michael Cho, MD, MPH, one of the senior authors of this manuscript and a physician-researcher in the Channing Division of Network Medicine and Pulmonary and Critical Care Division. “Many patients with COPD experience self-blame, but they may be comforted to know that genetics does play a role in who ultimately develops the disease.”