University Of Tasmania

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A genome-wide association study in progressive multiple sclerosis

journal contribution
posted on 2023-05-17, 14:18 authored by Martinelli-Boneschi, F, Esposito, F, Brambilla, P, Lindstrom, E, Lavorgna, G, Jim StankovichJim Stankovich, Rodegher, M, Capra, R, Ghezzi, A, Coniglio, G, Colombo, B, Sorosina, M, Martinelli, V, Booth, D, Oturai, AB, Stewart, G, Harbo, HF, Kilpatrick, TJ, Hillert, J, Rubio, JP, Abderrahim, H, Wojcik, J, Comi, G

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.


Publication title

Multiple Sclerosis










Menzies Institute for Medical Research


Sage Publications Ltd.

Place of publication

United Kingdom

Rights statement

Copyright 2012 The Author(s)

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified