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

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.