Major Collaboration Uncovers Surprising New
Genetic Clues to Diabetes
Analysis Identifies Potential New Therapeutic Targets; Suggests
Possible Ties to Prostate Cancer
An international team that included scientists from the National
Human Genome Research Institute (NHGRI), part of the National Institutes
of Health (NIH), today reported it has identified six more genetic
variants involved in type 2 diabetes, boosting to 16 the total
number of genetic risk factors associated with increased risk of
the disease. None of the genetic variants uncovered by the new
study had previously been suspected of playing a role in type 2
diabetes. Intriguingly, the new variant most strongly associated
with type 2 diabetes also was recently implicated in a very different
condition: prostate cancer.
The unprecedented analysis, published today in the advance online
edition of Nature Genetics, combined genetic data from more than
70,000 people. The work was carried out through the collaborative
efforts of more than 90 researchers at more than 40 centers in
Europe and North America.
"None of the genes we have found was previously on the radar
screen of diabetes researchers," said one of the paper’s senior
authors, Mark McCarthy, M.D., of the University of Oxford in England. "Each
of these genes, therefore, provides new clues to the processes
that go wrong when diabetes develops, and each provides an opportunity
for the generation of new approaches for treating or preventing
this condition."
When considered individually, the genetic variants discovered
to date account for only small differences in the risk of developing
type 2 diabetes. But researchers say when all of the variants are
analyzed together, some significant differences in risk are likely
to emerge. "By combining information from the large number
of genes now implicated in diabetes risk, it may be possible to
use genetic tools to identify people at unusually high or low risk
of diabetes. However, until we know how to use this information
to prompt beneficial changes in people’s treatment or lifestyle,
widespread genetic testing would be premature," said another
senior author, David Altshuler, M.D., Ph.D., of Massachusetts General
Hospital in Boston and the Broad Institute of Massachusetts Institute
of Technology and Harvard in Cambridge, Mass.
Type 2 diabetes affects more than 200 million people worldwide,
including nearly 21 million people in the United States. Previously
known as adult-onset, or non-insulin dependent diabetes (NIDDM),
type 2 diabetes usually appears after age 40, often in overweight,
sedentary people. However, a growing number of younger people and
even children are developing the disease.
Diabetes is a major cause of heart disease and stroke in U.S.
adults, as well as the most common cause of blindness, kidney failure
and amputations not related to trauma. Type 2 diabetes is characterized
by the resistance of target tissues to respond to insulin, which
controls glucose levels in the blood; and a gradual failure of
insulin-secreting cells in the pancreas.
"These new variants, along with other recent genetic findings,
provide a window into disease causation that may be our best hope
for the next generation of therapeutics. By pinpointing particular
pathways involved in diabetes risk, these discoveries can empower
new approaches to understanding environmental influences and to
the development of new, more precisely targeted drugs," said
NHGRI Director Francis S. Collins, M.D., Ph.D., who is a co-author
of the study. Dr. Collins' laboratory is a participant in the Finrisk
2002 and Finland-United States Investigation of NIDDM Genetics
(FUSION), which were among the studies that contributed data to
the new analysis. FUSION is funded by NHGRI’s Division of Intramural
Research and the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK).
Researchers said more work is needed to understand the impact
of their discovery that a genetic variant called JAZF1 appears
to be involved in diabetes as well as prostate cancer. One of the
study’s lead authors, Eleftheria Zeggini, Ph.D., of the University
of Oxford, said, "This is now the second example of a gene
which affects both type 2 diabetes and prostate cancer. We don’t
yet know what the connections are, but this may have important
implications for the future design of drugs for both of these conditions."
The research was conducted by the DIAbetes Genetics Replication
And Meta-analysis (DIAGRAM) consortium, which brought together
many groups active in the field of diabetes research. In the Nature
Genetics paper, DIAGRAM researchers combined the data from three
previously published genome-wide association studies in an effort
to boost the statistical power of their searches — an approach
that scientists refer to as meta-analysis. The strategy paid off,
enabling researchers to identify six genetic variants associated
with type 2 diabetes that had gone undetected in the smaller, individual
studies.
For more information about genome-wide association studies, go
to www.genome.gov/20019523.
For more information about diabetes, go to http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm.
NHGRI is one of 27 institutes and centers at NIH, an agency of
the Department of Health and Human Services. The NHGRI Division
of Intramural Research develops and implements technology to understand,
diagnose and treat genomic and genetic diseases. For more, visit www.genome.gov.
NIDDK, part of NIH, conducts and supports research on diabetes;
endocrine and metabolic diseases; digestive diseases, nutrition,
and obesity; and kidney, urologic and hematologic diseases. Spanning
the full spectrum of medicine and afflicting people of all ages
and ethnic groups, these diseases encompass some of the most common,
severe, and disabling conditions affecting Americans. For more
information about NIDDK and its programs, see www.niddk.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
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