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The Genetics of Multiple Sclerosis

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Molecular Basis of Multiple Sclerosis

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 51))

Abstract

After many years of slow progress in the genetic analysis of complex diseases, including multiple sclerosis (MS), the past few years have eventually seen the first steps of turning a frustrating quest into a success story with the identification of a rapidly increasing number of confirmed disease promoting or protecting genetic variants. The principal reason for the change in situation is numbers: number of individuals assessed in the studies and number of genetic variations available for genotyping. In short, we now know that it takes thousands of patients to identify new genes but also to pinpoint the complex interplay of several genetic factors within the strongest genetic locus in MS, the HLA gene complex. However, the mission is not completed until the gene identification has been translated into useful understanding of disease mechanisms, and this is likely to necessitate further methodological progress as well as hard work in functional studies. Obviously, the reason for gene identification is never going to be genetic counseling or prenatal diagnosis as not even full knowledge of the genetic background on MS will allow even 30% accuracy in disease prediction, i.e., the concordance rate in female monozygotic twins. Therefore, it is only in the way that risk genes reveal details of disease triggering events, or that severity genes influence mechanisms driving the tissue damage, that genetic information is likely to be useful.

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Abbreviations

CNS:

Central nervous system

EAE:

Experimental autoimmune encephalomyelitis

GWAS:

Genome wide association study

HLA:

Human leukocyte antigen

LD:

Linkage disequilibrium

MHC:

Major histocompatibility complex

MS:

Multiple sclerosis

QTL:

Quantitative trait locus

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  1. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

    Jan Hillert

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  1. Jan Hillert
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  1. Institut für Neuroimmunologie und, Klinische Multiple-Sklerose-Forschung, Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, Hamburg, 20251, Germany

    Roland Martin

  2. , Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, Innsbruck, 6020, Austria

    Andreas Lutterotti

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Hillert, J. (2009). The Genetics of Multiple Sclerosis. In: Martin, R., Lutterotti, A. (eds) Molecular Basis of Multiple Sclerosis. Results and Problems in Cell Differentiation, vol 51. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_9013

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