title: Risk genes associated with pediatric-onset MS but not with monophasic acquired CNS demyelination.
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.
  
  
  CONCLUSIONS
  The previously reported 57 SNPs for adult-onset MS also confer increased susceptibility to pediatric-onset MS, but not to monophasic ADS.
authors.affiliation: 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.
authors.forename: E Daniëlle
authors.initials: ED
authors.lastname: van Pelt
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Mescheriakova
authors.forename: Nalia
authors.initials: N
authors.lastname: Makhani
authors.forename: Immy A
authors.initials: IA
authors.lastname: Ketelslegers
authors.forename: Rinze F
authors.initials: RF
authors.lastname: Neuteboom
authors.forename: Suman
authors.initials: S
authors.lastname: Kundu
authors.forename: Linda
authors.initials: L
authors.lastname: Broer
authors.forename: Cecile
authors.initials: C
authors.lastname: Janssens
authors.forename: Coriene E
authors.initials: CE
authors.lastname: Catsman-Berrevoets
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Brenda
authors.initials: B
authors.lastname: Banwell
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Rogier Q
authors.initials: RQ
authors.lastname: Hintzen
mesh_terms: D000293:Adolescent; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors