Scientists Use Shared Genome Data to Confirm SORL1 Gene Linked to Alzheimer's
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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 e4 (APO-e4) -- 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