TY - JOUR
T1 - Risk genes associated with pediatric-Onset MS but not with monophasic acquired CNS demyelination
AU - Daniëlle van Pelt, E.
AU - Mescheriakova, Julia Y.
AU - Makhani, Nalia
AU - Ketelslegers, Immy A.
AU - Neuteboom, Rinze F.
AU - Kundu, Suman
AU - Broer, Linda
AU - Janssens, Cecile
AU - Catsman-Berrevoets, Coriene E.
AU - Van Duijn, Cornelia M.
AU - Banwell, Brenda
AU - Bar-Or, Amit
AU - Hintzen, Rogier Q.
PY - 2013/12/3
Y1 - 2013/12/3
N2 - Objective: To investigate whether 57 genetic risk loci recently identified in a large-scale genomewide 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 nucleotidepolymorphisms (SNPs) to discriminate between children with MS and those with monophasic ADSwas moderate (area under the curve [AUC] = 0.64), but improved with the addition of sex andHLA-DRB1*15 (AUC = 0.70). The combined effect of 57 SNPs exceeded the effect of HLADRB1*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 susceptibilityto pediatric-onset MS, but not to monophasic ADS.
AB - Objective: To investigate whether 57 genetic risk loci recently identified in a large-scale genomewide 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 nucleotidepolymorphisms (SNPs) to discriminate between children with MS and those with monophasic ADSwas moderate (area under the curve [AUC] = 0.64), but improved with the addition of sex andHLA-DRB1*15 (AUC = 0.70). The combined effect of 57 SNPs exceeded the effect of HLADRB1*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 susceptibilityto pediatric-onset MS, but not to monophasic ADS.
UR - http://www.scopus.com/inward/record.url?scp=84892381360&partnerID=8YFLogxK
U2 - 10.1212/01.wnl.0000436934.40034eb
DO - 10.1212/01.wnl.0000436934.40034eb
M3 - Article
C2 - 24198294
AN - SCOPUS:84892381360
SN - 0028-3878
VL - 81
SP - 1996
EP - 2001
JO - Neurology
JF - Neurology
IS - 23
ER -