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miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS

Brooke Rhead1,2, Xiaorong Shao1, Jennifer S Graves3,4

  • 1Division of Epidemiology School of Public Health University of California Berkeley California.

Annals of Clinical and Translational Neurology
|June 19, 2019
PubMed
Abstract

Insights

MicroRNAs (miRNAs) are implicated in pediatric multiple sclerosis (ped-MS) pathogenesis. GWAS analysis revealed miRNA-target gene signals associated with immune pathways, suggesting their role in ped-MS development.

Area of Science:

  • Genetics
  • Immunology
  • Neuroscience

Background:

  • Pediatric multiple sclerosis (ped-MS) accounts for 5% of MS cases.
  • Epigenetic factors, including microRNAs (miRNAs), are implicated in MS pathogenesis.
  • Early-onset MS may involve a higher genetic risk burden, potentially increasing miRNA dysregulation's role.

Purpose of the Study:

  • To investigate the role of miRNA dysregulation in pediatric multiple sclerosis (ped-MS) pathogenesis.
  • To identify specific miRNA-target gene interactions and pathways involved in ped-MS.

Main Methods:

  • Genome-wide association study (GWAS) data from 486 ped-MS cases and 1362 controls were analyzed.
  • MIGWAS software was used to evaluate enrichment of miRNA-target gene network signals.
  • Single nucleotide polymorphisms (SNPs) in miRNA genes and target binding sites (miR-SNPs) were tested for association with ped-MS.

Main Results:

  • GWAS analysis showed enrichment of miRNA-target gene signals (P=0.038).
  • 39 candidate miRNA-target gene pairs were identified, including those involved in immune and neuronal signaling.
  • miR-SNP analysis implicated five pathways, primarily immune signaling, in miRNA binding to target genes.

Conclusions:

  • GWAS findings suggest miRNAs contribute to ped-MS pathogenesis via immune signaling and other pathways.
  • Identified candidate miRNA-target gene pairs warrant further investigation for clinical applications.
  • miRNA dysregulation is a potential factor in the development of pediatric multiple sclerosis.

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