An international consortium of 175 scientists from 126 centers in the United States, Europe, and Australia identified sixteen common genetic variants associated with the function of the human lung. Their discovery sheds new light on the molecular basis of lung diseases such as chronic obstructive pulmonary disease (COPD) and identifies pathways that could be targeted by drugs.
Several University of Washington scientists were among the authors on this report published September 25
in Nature Genetics
. .Dr. Sina Gharib, an assistant professor of medicine, Division of Pulmonary and Critical Care, was one of the lead co-authors of the paper. He is a researcher at the UW Center for Lung Biology, and practices pulmonary and sleep medicine at Harborview Medical Center. Other UW investigators included Dr. Kristin Marciante, research scientist, Dr. Bruce Psaty, professor of medicine and epidemiology, and Dr. Susan Heckbert, professor of epidemiology.
The pioneering research involved a study of 2.5 million genetic variants in each of 48,201 people across the world. A smaller number of the most promising variants were then studied in a further 46,411 individuals. This study represents the largest investigation to date of the genetic basis of lung function in humans.
The recent discoveries build on research published by the same authors last year in Nature Genetics. The total number of genetic variants associated with lung function is now 26.
“A highlight of this project was the confirmation that many of the genes identified were expressed in various types of lung cells,”Gharib said. “This finding helps to confirm the importance of the genetic associations.
All subjects had their lung function measured using a spirometer, which is a simple device that records the volume of air a person can breathe out. In several pulmonary disorders, including COPD and asthma, narrowing of the airways can result in airflow obstruction as measured by a spirometer. These lung function measurements were evaluated for their association with common variations in each subject’s genome.
The findings from this study have several scientific and clinical implications. By providing insight into the genetic basis of normal lung function, the study results open new venues for research into the developmental biology of the respiratory system.
Importantly, identification of novel genes associated with the functional status of the lung can implicate mechanisms that lead to lung function decline in disorders such as COPD. Understanding these faulty mechanisms can guide the development of new therapies targeting these pathways.
“From a clinical standpoint,” Gharib noted, “these genetic discoveries may prove to be useful in screening individuals highly susceptible to lung function decline, particularly among smokers. Nevertheless, he and the other researchers emphasize that stopping smoking is the best way to prevent COPD. Ultimately, understanding the genetic basic of lung function and its impairment may contribute to efforts under way to reduce the burden of lung disease worldwide.