Multiple sclerosis genetics: leaving no stone unturned

Genes Immun. 2005 Aug;6(5):375-87. doi: 10.1038/sj.gene.6364237.


Compelling epidemiologic and molecular data indicate that genes play a primary role in determining who is at risk for developing multiple sclerosis (MS), how the disease progresses, and how someone responds to therapy. The genetic component of MS etiology is believed to result from the action of allelic variants in several genes. Their incomplete penetrance and moderate individual effect probably reflects epistatic interactions, post-transcriptional regulatory mechanisms, and significant environmental influences. Equally significant, it is also likely that locus heterogeneity exists, whereby specific genes influence susceptibility and pathogenesis in some individuals but not in others. With the aid of novel analytical algorithms, the combined study of genomic, transcriptional, proteomic, and phenotypic information in well-controlled study groups will define a useful conceptual model of pathogenesis and a framework for understanding the mechanisms of action of existing therapies for this disorder, as well as the rationale for novel curative strategies.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity / genetics*
  • Chromosome Mapping
  • Chromosomes, Human / genetics*
  • Epistasis, Genetic
  • Genetic Linkage*
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Humans
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / therapy
  • Proteomics
  • Signal Transduction / genetics
  • Signal Transduction / immunology