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Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease
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Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease
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Journal Article
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease
2011
Overview
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with considerable evidence suggesting an initiation of disease in the entorhinal cortex and hippocampus and spreading thereafter to the rest of the brain. In this study, we combine genetics and imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed study. To identify genetic susceptibility loci for AD, we conducted a genome-wide study of atrophy in regions associated with neurodegeneration in this condition. We identified one single-nucleotide polymorphism (SNP) with a disease-specific effect associated with entorhinal cortical volume in an intron of the
ZNF292
gene (rs1925690;
P
-value=2.6 × 10
−8
; corrected
P
-value for equivalent number of independent quantitative traits=7.7 × 10
−8
) and an intergenic SNP, flanking the
ARPP-21
gene, with an overall effect on entorhinal cortical thickness (rs11129640;
P
-value=5.6 × 10
−8
; corrected
P
-value=1.7 × 10
−7
). Gene-wide scoring also highlighted
PICALM
as the most significant gene associated with entorhinal cortical thickness (
P
-value=6.7 × 10
−6
).
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adult and adolescent clinical studies
/ Alzheimer Disease - genetics
/ Alzheimer Disease - pathology
/ Apolipoprotein E4 - genetics
/ Atrophy
/ Biological and medical sciences
/ Entorhinal Cortex - pathology
/ Female
/ Genes
/ Genetic Predisposition to Disease
/ Genetics
/ Genome-Wide Association Study
/ Genomes
/ Humans
/ Introns
/ Male
/ Medicine
/ Monomeric Clathrin Assembly Proteins - genetics
/ Nerve Tissue Proteins - genetics
/ Organic mental disorders. Neuropsychology
/ Polymorphism, Single Nucleotide
/ Psychology. Psychoanalysis. Psychiatry
