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Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease |
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| Authors: | Becky Inkster Anil W RaoKhanum Ridler Nicola Filippini Brandon WhitcherThomas E Nichols Sally WettenRachel A Gibson Michael BorrieAndrew Kertesz Danilo A GuzmanInge Loy-English Julie WilliamsPhilipp G Saemann Dorothee P AuerFlorian Holsboer Federica TozziPierandrea Muglia Emilio Merlo-PichPaul M Matthews |
| Institution: | a GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital, London, United Kingdom b Department of Clinical Neuroscience, Imperial College, London, United Kingdom c Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom d LENITEM, Laboratory of Epidemiology, Neuroimaging and Telemedicine-IRCCS, S. Giovanni di Dio-FBF, Brescia, Italy e Department of Psychiatry, University of Oxford, Oxford, United Kingdom f GlaxoSmithKline, Harlow, United Kingdom g University of Western Ontario, London, ON, Canada h University of Ottawa, Ottawa, ON, Canada i MRC Neuropsychiatric Genetics Group, School of Medicine, Cardiff University, Cardiff, United Kingdom j Max Planck Institute of Psychiatry, Munich, Germany k Genetics Division, Drug Discovery, Medicine Development Centre, GlaxoSmithKline, Research and Development, Verona, Italy l Experimental Medical Science, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Verona, Italy |
| 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. |
| Keywords: | Voxel-based morphometry Prefrontal cortex Alzheimer's disease GOLM1 Genetic association |
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