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Neurology. 2013 Dec 3;81(23):1996-2001. doi: 10.1212/01.wnl.0000436934.40034eb. Epub 2013 Nov 6.

Risk genes associated with pediatric-onset MS but not with monophasic acquired CNS demyelination.

Author information

1
From the Departments of Neurology (E.D.v.P., J.Y.M., I.A.K., R.F.N., C.E.C.-B., R.Q.H.) and Epidemiology (S.K., L.B., C.J., C.M.v.D.), Erasmus MC, Rotterdam, the Netherlands; the Departments of Pediatrics and Neurology (N.M.), Yale School of Medicine, New Haven, CT; the Department of Epidemiology (C.J.), Emory University, Atlanta, GA; the Department of Neurology (B.B.), Children's Hospital of Philadelphia, PA; the Division of Neurology (B.B.), Hospital for Sick Children and University of Toronto; and Montreal Neurological Institute (A.B.-O.), McGill University, Canada.

Abstract

OBJECTIVE:

To investigate whether 57 genetic risk loci recently identified in a large-scale genome-wide association study in adult patients with multiple sclerosis (MS) are also associated with a risk for pediatric-onset MS and whether they can predict MS diagnosis in children presenting with acquired demyelinating syndromes (ADS).

METHODS:

We included 188 children with ADS, of whom 53 were diagnosed with MS, 466 patients with adult-onset MS, and 2,046 adult controls in our cohort study. Weighted genetic risk scores (wGRS) were calculated to evaluate genetic effects.

RESULTS:

Mean wGRS was significantly higher for patients with pediatric-onset MS (7.32 ± 0.53) as compared with patients with monophasic ADS (7.10 ± 0.47, p = 0.01) and controls (7.11 ± 0.53, p < 0.01). We found no difference in mean wGRS of participants with monophasic ADS (7.10 ± 0.47) and controls (7.11 ± 0.53). The ability of the wGRS for the 57 single nucleotide polymorphisms (SNPs) to discriminate between children with MS and those with monophasic ADS was moderate (area under the curve [AUC] = 0.64), but improved with the addition of sex and HLA-DRB1*15 (AUC = 0.70). The combined effect of 57 SNPs exceeded the effect of HLA-DRB1*15 alone in our risk models for pediatric- and adult-onset MS.

CONCLUSION:

The previously reported 57 SNPs for adult-onset MS also confer increased susceptibility to pediatric-onset MS, but not to monophasic ADS.

[Indexed for MEDLINE]

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