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Abstract

We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) (n=544). We observed an opposite relationship in the two disease courses: a higher weighted genetic risk score was associated with an earlier age at onset in BOMS (rho= −0.1; p=5 × 10⁻³) and a later age at onset in PrMS cases (rho=0.07; p=0.15) (p of difference of regression=1.4 × 10⁻²). These findings suggest that established MS risk variants anticipate the onset of the inflammatory phase, while they have no impact on, or even delay, the onset of the progressive phase.

Keywords

Primary-progressive relapsing–remitting multiple sclerosis age of onset weighted genetic risk score genetic risk

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References

Ebers

. Natural history of primary progressive multiple sclerosis. Mult Scler 2004; 10: 8–15.

International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham

Patsopoulos

. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 2013; 45: 1353–1360.

Harbo

Isobe

Berg-Hansen

. Oligoclonal bands and age at onset correlate with genetic risk score in multiple sclerosis. Mult Scler 2013; 20: 660–668.

Harding

Ingram

Cossburn

. Genotype-phenotype correlation for non-HLA disease associated risk alleles in multiple sclerosis. Neurosci Lett 2012; 526: 15–19.

Jensen

Stankovich

Van der Walt

. Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients. PLoS One 2010; 5: e10003.

International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer

. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 476: 214–219.

Poser

. The diagnosis and management of multiple sclerosis. Acta Neurol Scand 2005; 112: 199–201.

Sorosina

Brambilla

Clarelli

. Genetic burden of common variants in progressive and bout-onset multiple sclerosis. Mult Scler 2013; 20: 802–811.

De Jager

Chibnik

Cui

. Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: A weighted genetic risk score. Lancet Neurol 2009; 8: 1111–1119.

10.

Masterman

Ligers

Olsson

. HLA-DR15 is associated with lower age at onset in multiple sclerosis. Ann Neurol 2000; 48: 211–219.

11.

Scalfari

Neuhaus

Daumer

. Onset of secondary progressive phase and long-term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry 2014; 85: 67–75.

12.

Trojano

Pellegrini

Paolicelli

. Real-life impact of early interferon beta therapy in relapsing multiple sclerosis. Ann Neurol 2009; 66: 513–520.

13.

Isobe

Damotte

Lo Re

. Genetic burden in multiple sclerosis families. Genes Immun 2013; 14: 434–440.

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