Related Experiment Video

Updated: May 6, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
09:41

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis

Published on: July 19, 2019

12.4K

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

E Daniëlle van Pelt1, Julia Y Mescheriakova, Nalia Makhani

  • 1From 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.

Neurology
|November 8, 2013
PubMed

Insights

Genetic risk factors for adult multiple sclerosis (MS) also increase susceptibility in children with MS. These 57 genetic risk loci do not predict monophasic acquired demyelinating syndromes (ADS) in children.

Area of Science:

  • Genetics
  • Neurology
  • Pediatrics

Background:

  • Multiple sclerosis (MS) is a complex neurological disorder with a significant genetic component.
  • Genome-wide association studies (GWAS) have identified numerous genetic risk loci associated with adult-onset MS.
  • The genetic architecture of pediatric-onset MS (pMS) and its relationship with adult risk factors remain less understood.

Purpose of the Study:

  • To determine if 57 genetic risk loci identified in adult MS are associated with pediatric-onset MS (pMS).
  • To assess the predictive value of these genetic loci for MS diagnosis in children with acquired demyelinating syndromes (ADS).

Main Methods:

  • A cohort study including 188 children with ADS (53 diagnosed with MS), 466 adult-onset MS patients, and 2,046 adult controls.
  • Calculation of weighted genetic risk scores (wGRS) using 57 single nucleotide polymorphisms (SNPs) associated with adult MS.
  • Analysis of wGRS, sex, and HLA-DRB1*15 for prediction of MS in pediatric and adult cohorts.

Main Results:

  • Mean wGRS was significantly higher in pediatric-onset MS patients compared to monophasic ADS and controls.
  • No significant difference in wGRS was observed between monophasic ADS and controls.
  • The 57 SNPs showed moderate predictive ability for MS in children, improving with the addition of sex and HLA-DRB1*15 (AUC = 0.70).
  • The combined effect of the 57 SNPs exceeded that of HLA-DRB1*15 alone in risk models for both pediatric and adult MS.

Conclusions:

  • The 57 genetic risk loci identified for adult MS confer increased susceptibility to pediatric-onset MS.
  • These genetic factors do not appear to increase susceptibility to monophasic ADS in children.
  • Genetic risk profiling holds potential for improving MS diagnosis in pediatric populations.
Abstract

More Related Videos

Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines09:46

Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines

Published on: September 21, 2021

5.0K
A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

7.9K

Related Concept Videos

Multiple Sclerosis l: Introduction01:19

Multiple Sclerosis l: Introduction

Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
31
Pedigree Analysis01:35

Pedigree Analysis

Overview
78.9K
Sex-linked Disorders01:43

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
95.2K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
31.3K
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
12.7K
Genetic Lingo01:11

Genetic Lingo

Overview
84.9K