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Study Unveils Potential Genetic Links to Lung Disease Risk

By Robin Mackar
January 2010

Stephanie London, M.D., Dr.P.H.
London was principal investigator on the study by an international team of 28 scientists. (Photo courtesy of Steve McCaw)

First author Dana Hancock, Ph.D.
First author Dana Hancock, Ph.D., is a postdoctoral fellow in the NIEHS Genetics, Environment and Respiratory Disease Group headed by London. She recently received an NIH Fellows Award for Research Excellence. (Photo courtesy of Steve McCaw)

A new NIH-funded study involving data from more than 20,000 individuals has uncovered several DNA sequences linked to impaired pulmonary function. The research, an analysis that combined the results of several smaller studies, provides insight into the mechanisms involved in reaching full lung capacity. Published online in Nature Genetics, the findings may ultimately lead to a better understanding of lung function and diseases such as asthma and chronic obstructive pulmonary disease (COPD) - the fourth leading cause of death in the United States.

"We have known for a while that genetic factors put some people at risk for lower lung function - a factor in COPD and a risk for early mortality. But, we did not know which specific genetic regions were involved," said Stephanie London, M.D., Dr.P.H., NIEHS senior investigator and a senior author on the paper( Exit NIEHS. "These findings point to specific gene regions."

Findings may also offer insight into other diseases

Impaired lung function is a hallmark of COPD and other lung diseases( Exit NIEHS. But it is also linked to mortality from a wide range of other diseases, including cardiovascular disease and cancer. So knowing some of the genes involved is a first step toward understanding the relationship between lung function and mortality, as well as developing new interventions to manage lung diseases.

"Leveraging our investment in collecting these samples has led to new findings and will help focus future research efforts," said James P. Kiley, Ph.D., director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute (NHLBI).

The researchers used data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. CHARGE is an ongoing study - a group of groups - that combines genome-wide association study (GWAS) results from several population-based studies. Pooling data from many studies gives much greater power to find the specific genes involved than looking at any one study alone.

The study analyzed data from participants in four earlier large-cohort studies

The GWAS approach involves measuring hundreds of thousands of genetic variants, in thousands of individuals, in hopes of finding novel genetic variations associated with specific diseases or conditions.

This meta-analysis provided data from more than 20,000 participants. The individual studies included three US-based population studies supported by the NHLBI - the Artherosclerosis Risk in Communities, the Cardiovascular Health Study, and the Framingham Heart Study - and the Rotterdam Study in the Netherlands.

The researchers focused on finding genetic commonalities in DNA that lead to some people having lower lung function than others of the same age, gender, race, size, and smoking history.

One way researchers determine airflow obstruction is by using a machine called a spirometer to measure how much air a person breathes in and out, as well as how fast it is blown out, or expired. Spirometry is an important tool used to diagnose asthma, pulmonary fibrosis, cystic fibrosis, and COPD, as well as the impact of environmental exposure on lung health. In disease, the ratio between forced expiratory volume (FEV1) and forced vital capacity (FVC) - an indicator of airflow obstruction - is abnormally low.

Research has potential applications in environmental public health

"This is a beautiful example of how modern genomic approaches can unearth valuable new insights from previous research," said NIEHS/NTP Director Linda Birnbaum, Ph.D. "It sets us on a course for learning much more about how lung diseases develop and how environmental triggers like smoking and air pollution work in combination with genes."

Citation: Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, et al.( Exit NIEHS 2009. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nature Genetics. Online Dec. 13. doi:10.1038/ng.500

(Robin Mackar is the news director in the NIEHS Office of Communications and Public Liaison and a regular contributor to the Environmental Factor.)

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