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Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease

Inkster, Becky, Rao, Anil W., Ridler, Khanum, Filippini, Nicola, Whitcher, Brandon, Nichols, Thomas E., Wetten, Sally, Gibson, Rachel A., Borrie, Michael, Kertesz, Andrew, Guzman, Danilo A., Loy-English, Inge, Williams, Julie, Saemann, Philipp G., Auer, Dorothee P., Holsboer, Florian, Tozzi, Federica, Muglia, Pierandrea, Merlo-Pich, Emilio and Matthews, Paul M. 2012. Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease. Neurobiology of Aging 33 (3) , pp. 457-465. 10.1016/j.neurobiolaging.2010.04.018

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: voxel-based morphometry, prefrontal cortex, Alzheimer's disease, GOLM1, genetic association
Publisher: Elsevier
ISSN: 0197-4580
Last Modified: 04 Jun 2017 04:34
URI: http://orca.cf.ac.uk/id/eprint/41263

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