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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)).

Original publication

DOI

10.1038/mp.2010.123

Type

Journal article

Journal

Mol Psychiatry

Publication Date

11/2011

Volume

16

Pages

1130 - 1138

Keywords

Alzheimer Disease, Apolipoprotein E4, Atrophy, Brain, Carrier Proteins, Disease Progression, Entorhinal Cortex, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Hippocampus, Humans, Introns, Linkage Disequilibrium, Magnetic Resonance Imaging, Male, Monomeric Clathrin Assembly Proteins, Nerve Tissue Proteins, Organ Size, Phosphoproteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors