Use of Utah High-Risk, Extended Pedigrees for COPD Genetic Discovery

Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death in the U.S., is characterized by irreversible airflow limitations that lead to progressive pulmonary functional decline and death. COPD results from exposure of a genetically susceptible individual to environmental triggers, most significantly cigarette smoking. Notably, only an estimated 20% of smokers are diagnosed with COPD. Although it is not well understood why some smokers develop COPD and others don’t, inherited genetic factors are clearly important.

John Hoidal, MD, and Mary Beth Scholand, MD, have a long history of COPD research, during which time they helped to establish one of the most robust COPD data and biospecimen sets on the globe. This unique resource coupled with the Utah Population Database has enabled the investigators to assemble extended pedigrees that may hold secrets to the genetic determinants of COPD.

In the current study, the researchers are sequencing subjects from the most informative pedigrees, and using state-of-the-art data analysis tools to evaluate potential genetic determinants for COPD. Integral to the investigation is an innovative strategy utilizing pedigrees composed of smokers who developed COPD, contrasted to smokers who were protected from developing this disease. This powerful approach may yield the unique benefit of also revealing genetic factors that protect smokers from developing the disease.

The results of this work will not only accelerate development of personalized therapeutic interventions, but will also serve as a model for designing future studies exploring the intersection of genotype and environment.

Chronic Obstructive Lung Disease (COPD)

Chronic Obstructive Lung Disease (COPD) is an incurable disease that can be characterized primarily by chronic bronchitis or emphysema. Some patients have elements of both processes. With emphysema, normal lungs are destroyed by ongoing inflammation that breaks down the air sacs known as alveoli. With chronic bronchitis, the bronchioles are broken down and become filled with mucus. Both processes result in an inefficient lung that cannot exchange oxygen. Patients develop worsening shortness of breath as the disease progresses