Miller School genetic researchers
release new findings on Alzheimer�s disease
Researchers
at the Miller School of Medicine led by Margaret A. Pericak-Vance,
director of the Miami Institute for Human Genomics and the Dr. John T.
Macdonald Foundation Professor of Human Genomics, and Jonathan L.
Haines, at Vanderbilt University Medical Center, have identified nine
genes that may increase susceptibility for Alzheimer’s
disease and confirmed a region on chromosome 12q long believed to
harbor an Alzheimer’s risk gene. The findings were posted
online last week and will appear in the January issue of the "American
Journal of Human Genetics". The project represents the first essential
step in the application of modern genomic approaches to complex
diseases and is one of four studies of its kind.
A
research team at the Miller School’s Miami Institute for
Human Genomics and the Vanderbilt Center for Human Genetics Research
performed a genome-wide association study using state-of-the-art
genotyping technology that allows scientists to interrogate 550,000
genetic variations in approximately 500 people with
Alzheimer’s disease and 500 people without the disease. The
results were validated in an independent dataset.
“Results
from this study
open the door for increased understanding of this important
neurological disorder,” said Dr. Pericak-Vance, director of
the Miami
Institute for Human Genomics and the Dr. John T. Macdonald Foundation
Professor of Human Genomics. “We
now have exciting new directions to explore.”
The findings show that the
amyloid precursor protein, accepted as a risk gene for early-onset
Alzheimer’s disease, is also involved in late-onset
Alzheimer’s disease. The
study also provides evidence of a risk locus at 12q13.
Chromosome 12 has been of intense interest to geneticists
in search of Alzheimer’s risk genes.
The locus implicated by this study is in close proximity
to the vitamin D3 receptor gene. Low
vitamin D levels have been reported in patients with cognitive
impairment and Alzheimer’s disease.
A variation in the vitamin D3
receptor gene that causes low vitamin D levels may also increase risk
for Alzheimer’s disease. According
to Dr. Haines, “the vitamin D3 receptor finding on chromosome
12 is
really exciting because it implicates a potential biological pathway
that has been of interest in neurological disorders.”
For the past decade,
Alzheimer’s disease genetics has been at an impasse. In
the early 1990s, Dr. Pericak-Vance’s discovery of the
association of
apolipoprotein E with Alzheimer’s disease gave hope that the
genetic
etiology of a host of commons diseases would rapidly unravel. Scientists
were able to identify genes of large effect, because they are present
in a great enough portion of the population to be detected with
available technologies. Disease
genes present in smaller portions of the population, however, could not
be confirmed.
Genome-wide association studies have
improved researchers’ ability to find disease genes of
smaller or more moderate effect. Thanks
to this powerful new tool, there will be several new candidate genes to
pursue. “Data
from the Miami Institute for Human Genomics genome-wide association
study will invigorate the field and form a foundation for future
investigations into the genetics of Alzheimer’s
disease,” said
Pericak-Vance. “We
are now closely studying a number of candidate genes associated with
Alzheimer’s risk in our data.”
The identification of new
Alzheimer disease genes may lead to a better understanding of the
complex causes of Alzheimer’s disease and lead to improved
diagnostic
tools, enhanced preventive measures, and find new targets for treatment.
source: UM
Miller School of Medicine News