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Brain Advance Access published online on May 18, 2008
Brain, doi:10.1093/brain/awn081
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Review Article

The complex genetics of multiple sclerosis: pitfalls and prospects

Stephen Sawcer

University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's, Hospital, Hills Road, Cambridge, CB2 2QQ, UK

Correspondence to: Stephen Sawcer, University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's, Hospital, Hills Road, Cambridge, CB2 2QQ, UK E-mail: sjs1016{at}mole.bio.cam.ac.uk

The genetics of complex disease is entering a new and exciting era. The exponentially growing knowledge and technological capabilities emerging from the human genome project have finally reached the point where relevant genes can be readily and affordably identified. As a result, the last 12 months has seen a virtual explosion in new knowledge with reports of unequivocal association to relevant genes appearing almost weekly. The impact of these new discoveries in Neuroscience is incalculable at this stage but potentially revolutionary. In this review, an attempt is made to illuminate some of the mysteries surrounding complex genetics. Although focused almost exclusively on multiple sclerosis all the points made are essentially generic and apply equally well, with relatively minor addendums, to any other complex trait, neurological or otherwise.

Key Words: multiple sclerosis; genetics; association, linkage

Abbreviations: GWAS, Genome-Wide Association Study; HLA, human leucocyte antigens; IL2R, interleukin-2 receptor; IL7R, interleukin-7 receptor; IMAGEN, International MHC and Autoimmunity Genetics Network; IMSGC, International Multiple Sclerosis Genetics Consortium; LD, linkage disequilibrium; MHC, major histocompatibility complex; MAF, minor allele frequency; NIMH, National Institutes of Mental Health; nsSNPs, non-synonymous single nucleotide polymorphism; RAF, risk allele frequency; SNP, single nucleotide polymorphism; WTCCC, Wellcome Trust Case Control Consortium

Received March 10, 2008. Revised March 27, 2008. Accepted April 2, 2008.


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