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A genome-wide association study in progressive multiple sclerosis


Martinelli-Boneschi, F and Esposito, F and Brambilla, P and Lindstrom, E and Lavorgna, G and Stankovich, J and Rodegher, M and Capra, R and Ghezzi, A and Coniglio, G and Colombo, B and Sorosina, M and Martinelli, V and Booth, D and Oturai, AB and Stewart, G and Harbo, HF and Kilpatrick, TJ and Hillert, J and Rubio, JP and Abderrahim, H and Wojcik, J and Comi, G, A genome-wide association study in progressive multiple sclerosis, Multiple Sclerosis, 18, (10) pp. 1384-1394. ISSN 1352-4585 (2012) [Refereed Article]

Copyright Statement

Copyright 2012 The Author(s)

DOI: doi:10.1177/1352458512439118


Background: The role played by genetic factors in influencing the clinical course of multiple sclerosis (MS) is not yet well established.

Objective: We aimed to identify genetic variants associated with progressive MS (PrMS).

Methods: We conducted a genome-wide association study (GWAS) in 197 patients with PrMS and 234 controls of Italian origin. We tested the top 20 single nucleotide polymorphisms (SNPs) with suggestive evidence of association (p-value < 10−4) in two independent sets of primary progressive MS cases and controls.

Results: We identified a risk-associated SNP in the HLA region in linkage disequilibrium (LD) with DRB1*1501 and DQB*0602 loci, with genome-wide significance (rs3129934T, pcombined = 6.7×10-16, OR = 2.34, 95% CI = 1.90–2.87), and a novel locus on chromosome 7q35 with suggestive evidence of association (rs996343G, pcombined = 2.4×10-5, OR = 0.70, 95% CI = 0.59–0.83) which maps within a human endogenous retroviral (HERV) element. The new locus did not have a ‘cis’ effect on RNA expression in lymphoblastic cell lines, but pathway analyses of ‘trans’ effects point to an expression regulation of genes involved in neurodegeneration, including glutamate metabolism (p < 0.01) and axonal guidance signalling (p < 0.02).

Conclusions: We have confirmed the established association with the HLA region and, despite the low statistical power of the study, we found suggestive evidence for association with a novel locus on chromosome 7, with a putative regulatory role.

Item Details

Item Type:Refereed Article
Keywords:multiple sclerosis, association studies in genetics, single nucleotide polymorphism, genome-wide association study, primary progressive
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Stankovich, J (Dr Jim Stankovich)
ID Code:80852
Year Published:2012
Web of Science® Times Cited:39
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-11-14
Last Modified:2017-11-06

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