Multiple Sclerosis (MS): Genetics

DA Dyment, University of Ottawa, Ottawa, Canada
GC Ebers, University of Oxford, Oxford, UK

Published online: December 2011

DOI: 10.1002/9780470015902.a0005562.pub2

Full Article on Wiley Online Library

Multiple sclerosis (MS) is a complex trait and highlights the interplay between nature, nurture and the stochastic events of development. Genetic-epidemiological studies have shown the importance of the genetic contribution to the marked familial clustering of MS. Environmental factors also increase MS risk and act at a population-based level. Climate and the subsequent effect on vitamin D levels are thought to play an important role. There is a clear association with MS and human leukocyte antigen (HLA) polymorphisms located at chromosome 6p21. Individuals who carry the at-risk genotypes (DRB1^*15/15) have a five- to sixfold increased chance of MS. Genome-wide searches for other non-HLA susceptibility genes by association have been successful in identifying many disease genes of mild effects. The genes implicated have an immune-related function. There are likely additional genes contributing to MS risk and new technologies may prove fruitful for their identification.

Key Concepts:

Genetic-epidemiological studies have shown the importance of genes to MS risk and studies such as twin, adoptive and half-siblings are useful tools in the study of complex traits.
The search for genes in complex traits is difficult and often requires hundreds to thousands of cases and unaffected controls. This is due to the small effect of any given risk gene.
A risk-related gene may be modified by its interaction with other genes and the environment and may be further modified by chance developmental processes.

Keywords: multiple sclerosis; nature and nurture; complex trait; human leukocyte antigen; multifactorial disease

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Article Title:	Multiple Sclerosis (MS): Genetics
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	Figure 1. HLA genotypic MS risks. (Reproduced with permission from Ramagopalan et al., 2007.)
	Figure 2. A graphic representation of the T-helper cell differentiation pathway and genes associated with multiple sclerosis. (From International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium, 2011; reproduced with permission from Nature Publishing Group.)

Multiple Sclerosis (MS): Genetics

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