The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years

Trends Genet. 2017 Dec;33(12):960-970. doi: 10.1016/j.tig.2017.09.004. Epub 2017 Oct 5.


Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. Here, we present a historical perspective on the progress made in MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility. Such a model necessarily includes a better understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment. Future genetic studies in MS will likely focus on the role of rare variants and endophenotypes.

Keywords: GWAS; gene regulatory networks; genetic pathways; multiple sclerosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics*
  • Genome-Wide Association Study / methods
  • Humans
  • Multiple Sclerosis / genetics*
  • Phenotype