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NIH
researchers discover DNA sequences related to lung function
01-11-2010
EDIT CONNECT
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BETHESDA, Md.—Treating disease needs to be about
tracking
down root causes more than just treating symptoms as was the case for so much
of medical history, and researchers with the National Institutes of Health (NIH)
have made a solid step along that path with a new
study involving data from
more than 20,000 individuals that has uncovered several DNA sequences linked to
impaired pulmonary function and that shine a
light on genetic links to lung
disease risk.
In this case, in research published online for Nature
Genetics on Dec. 13—in an article titled
"Meta-analyses of genome-wide association studies identify multiple loci
associated with pulmonary function"—the scientists combined the results of
several smaller studies, thus providing insight into the mechanisms that play
into people reaching full lung capacity.
The researchers anticipate that the findings may ultimately
lead to better understanding of lung function in general, but also
shine a more
specific light on such diseases as chronic obstructive pulmonary disease
(COPD), the fourth leading cause of death in the United States,
as well as
diseases like asthma and perhaps lung cancer in some patients.
"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," says Dr. Stephanie
London, a senior investigator at the National
Institute of
Environmental Health Sciences (NIEHS), and a senior author on the
paper. "But, we did not know which specific genetic regions were involved.
These
findings point to specific gene regions."
After submitting the initial draft of the paper, she says,
the reviewers
asked London and her team to also crunch the numbers after taking
out patients with asthma, COPD and the like—essentially removing the people who
were
most informative because they had the most genetic associations that were
relevant to the research. But in the end, London says, that exercise was indeed
useful, as it showed that her team's significant findings still had
significance, even in the populations with healthier lung function.
"This has given us confidence that what we have found
actually does influence lung function across
normal and diseased populations,"
London says.
Impaired lung function is a hallmark of COPD and
other lung
diseases, but London points out that it is also linked to mortality in many
other diseases, such as cardiovascular disease and cancer.
Because of this,
having an understanding of at least some of the genes involved in lung function
is a first step toward defining the relationship
between lung function and
mortality. This knowledge, in turn, will help in the development of new
screening tools, diagnostic tools and therapies to
identify, monitor and manage
lung diseases.
"Leveraging our investment in collecting these
samples has
led to new findings and will help focus future research efforts," says Dr.
James P. Kiley, director of the Division of Lung Diseases at
the National
Heart, Lung, and Blood Institute (NHLBI).
To conduct the analysis published in Nature Genetics, the researchers used data from the
Cohorts for
Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. CHARGE is
an ongoing study 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 NIH reports. The individual studies included three U.S.-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.
According to London, her team 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.
"This is a beautiful example of how modern genomic
approaches can unearth valuable new insights from previous research," says Dr.
Linda Birnbaum,
director of the NIEHS. "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."
Another researcher involved with the consortium
recently
received follow-up funding from the NHLBI to do deep sequencing around the
kinds of "top hits" like London and her team found. There is no
assurance that
that sequencing work will involve the pulmonary hits that London and her colleagues
found, but she says she has submitted her study for
possible inclusion with
that sequencing effort.
It would be a huge boost to her team's work if it was
part
of that sequencing effort, London notes, because what often isn't picked up in
work like hers are the rare genetic variants that have smaller
signal strength
and don't show up as well. Because, while the more common genetic variants she
has found are important leads, it may turn out the true
cause of morbidity and
mortality in many cases lies more in how those common variants interact with
rare variants, she notes.
Additional research going forward that London plans to
pursue includes getting a larger data set to find genetic variants
with smaller
effects than the ones she and her team identified, and to do more studies on
gene-environment interactions with pulmonary function and
lung disease.
Code: E01131004 Back |
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