Scientists Use Shared Genome Data To Confirm
SORL1 Gene Linked to Alzheimer's
Until recently, only one of the approximately 30,000 genes in
the human genome has been linked to risk of late-onset Alzheimer's
disease (AD). Now, a new NIH-supported study in the Nov. 19, 2007,
issue of NeuroReport (now online) used a publicly shared
genome dataset to strongly support findings that variation in the
sequence of the SORL1 gene may be a second risk factor gene for
late-onset disease. Identifying the genes involved in AD ultimately
may help determine who may be at greater risk and enable researchers
to zero in on pathways to develop new treatments.
The National Institute on Aging (NIA), part of the National Institutes
of Health (NIH), funded the study, along with the Canadian Institutes
of Health Research and a number of private foundations in the U.S.,
Canada and Japan.
Three mutated genes — amyloid precursor protein (APP) and
the presenilins (PS1 and PS2) — have been shown to cause
rare, early-onset, familial forms of the disease which mostly occur
in middle age. A gene variant — apolipoprotein ε4
(APO-ε4) — was the first confirmed risk factor for
the common form of late-onset AD, which typically occurs after
age 65.
Earlier this year, researchers first linked variations in the
gene SORL1 to late-onset AD. The analysis involved 14 collaborating
institutions in North America, Europe and Asia, and 6,600 people
who donated blood and tissue for genetic typing. To learn more,
go to http://www.nia.nih.gov/NewsAndEvents/PressReleases/PR20070114SORL1gene.htm.
This new study confirms those findings and in a novel way. Lindsay
A. Farrer, Ph.D., of the Boston University School of Medicine and
colleagues accessed data from a genome-wide association study (GWAS)
recently made publicly available online by the Translational Genomics
Research Institute (TGen), a nonprofit research institute promoting
genomics research. GWAS involves rapidly scanning for markers across
the complete set of DNA of many people to find genetic variations
related to a particular disease. By analyzing TGen's data on the
DNA of 1,408 cases and controls, Dr. Farrer's study replicated
the findings of the earlier studies that linked SORL1 data to late-onset
AD.
"These results are especially remarkable since this gene
was not a focus of the original TGen study which generated the
data used to test our hypothesis," Farrer said.
"This is the first example of publicly available data from
a genome-wide association study to confirm the identification of
a risk factor gene," said Marcelle Morrison-Bogorad, Ph.D.,
director of the Neuroscience and Neuropsychology Program at NIA. "This
shows the tremendous benefit of highly collaborative interaction
and rapid data sharing. Sample sharing greatly increases the likelihood
of finding new risk factor genes relatively quickly and inexpensively."
Collaboration was a hallmark of the study, with TGen conducting
the GWAS using brain tissues and blood samples made available by
NIA Alzheimer Center brain banks, NIA-funded investigators, and
other collaborating institutes. The Boston University Linux Cluster
for Genetic Analysis, funded by the National Center for Research
Resources (NCRR) at the NIH, provided Dr. Farrer's group high-speed
computer analysis.
NIA leads the federal effort on understanding the biomedical,
social and behavioral aspects of aging and the problems of older
people by conducting and supporting research into these areas.
For more information on aging-related research and the NIA, please
visit www.nia.nih.gov. The
NIA provides information on age-related cognitive change and neurodegenerative
disease specifically at its Alzheimer's Disease Education and Referral
(ADEAR) Center site at www.nia.nih.gov/alzheimers.
To sign up for e-mail alerts about new findings or publications
about aging or age-related cognitive decline, please visit either
Web site.
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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