Genetic associations with brain cortical thickness in multiple sclerosis

Matsushita, T. and Madireddy, L. and Sprenger, T. and Khankhanian, P. and Magon, S. and Naegelin, Y. and Caverzasi, E. and Lindberg, R. L. and Kappos, L. and Hauser, S. L. and Oksenberg, J. R. and Henry, R. and Pelletier, D. and Baranzini, S. E.. (2015) Genetic associations with brain cortical thickness in multiple sclerosis. Genes, Brain and Behavior, 14 (2). pp. 217-227.

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Official URL: https://edoc.unibas.ch/62324/

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Multiple sclerosis (MS) is characterized by temporal and spatial dissemination of demyelinating lesions in the central nervous system. Associated neurodegenerative changes contributing to disability have been recognized even at early disease stages. Recent studies show the importance of gray matter damage for the accrual of clinical disability rather than white matter where demyelination is easily visualized by magnetic resonance imaging (MRI). The susceptibility to MS is influenced by genetic risk, but genetic factors associated with the disability are not known. We used MRI data to determine cortical thickness in 557 MS cases and 75 controls and in another cohort of 219 cases. We identified nine areas showing different thickness between cases and controls (regions of interest, ROI) (eight of them were negatively correlated with Kurtzke's expanded disability status scale, EDSS) and conducted genome-wide association studies (GWAS) in 464 and 211 cases available from the two data sets. No marker exceeded genome-wide significance in the discovery cohort. We next combined nominal statistical evidence of association with physical evidence of interaction from a curated human protein interaction network, and searched for subnetworks enriched with nominally associated genes and for commonalities between the two data sets. This network-based pathway analysis of GWAS detected gene sets involved in glutamate signaling, neural development and an adjustment of intracellular calcium concentration. We report here for the first time gene sets associated with cortical thinning of MS. These genes are potentially correlated with disability of MS.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Neuroimmunology (Derfuss/Lindberg)
UniBasel Contributors:Lindberg Gasser, Raija L.P.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley-Blackwell - STM
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Nov 2018 17:09
Deposited On:19 Nov 2018 17:09

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