Multiple sclerosis: the environment and causation

Curr Opin Neurol. 2007 Jun;20(3):261-8. doi: 10.1097/WCO.0b013e32815610c2.


Purpose of review: We review current thinking on the aetiology of multiple sclerosis, how genetic susceptibility interacts with environmental risk factors at the population level, multiple sclerosis-associated risk factors and contemporary causation theory.

Recent findings: Two large genomic studies have confirmed the unambiguous associations with the DRB1 and DQB alleles of the human leucocyte antigen class II region. No other region with genome-wide significance has been identified. Family-based genetic epidemiological approaches have found no evidence of nongenetic transmissibility. This indicates that the action of the environment in influencing multiple sclerosis risk is operative at a macroenvironmental or population level, and not within families or the microenvironment. Environmental factors receiving renewed attention include vitamin D status, Epstein-Barr virus infection and smoking. Bradford Hill's criteria for causation have been modified and should be adopted as a framework for demonstrating causation in relationship to multiple sclerosis.

Summary: Multiple sclerosis is a complex disease because of interaction between genes and the environment. Any theory of causation for a specific agent will have to be congruent with the biology of the disease.

Publication types

  • Review

MeSH terms

  • Causality
  • Disease Transmission, Infectious
  • Environmental Exposure / adverse effects*
  • Epstein-Barr Virus Infections / complications
  • Genetic Predisposition to Disease / genetics*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Multiple Sclerosis / epidemiology*
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Risk Factors
  • Smoking / adverse effects
  • Vitamin D Deficiency / complications


  • HLA Antigens