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Replications of the association between APOE-ε4 allele load and regional brain atrophy in Alzheimer's disease (AD) patients hold promise for future studies testing relationships between other disease risk gene variants and brain structure. A polymorphism, rs10868366, in the Golgi phosphoprotein 2 gene, GOLM1, was recently identified as an AD risk factor in a genome-wide association study. In a subset of the same AD cohort, we used voxel-based morphometry to test for association between the disease risk genotype and reduced regional gray matter (GM) volume in AD patients (n = 72). A mean 14% reduction in GM volume was observed in the left frontal gyrus with the higher risk GG genotype. A similar association was observed in an independent, dataset of nondemented subjects (n = 278), although with a smaller effect (1%). This replicated association with GM structural variation suggests that GOLM1 polymorphisms may be related to cognitive phenotypes. The greater effect size in AD patients also suggests that the GG genotype could be a risk factor for the expression of cognitive deficits in AD.

Original publication

DOI

10.1016/j.neurobiolaging.2010.04.018

Type

Journal article

Journal

Neurobiol Aging

Publication Date

03/2012

Volume

33

Pages

457 - 465

Keywords

Adult, Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Cognitive Dysfunction, Female, Genetic Variation, Humans, Male, Membrane Proteins, Middle Aged, Prefrontal Cortex, Young Adult