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What role for genetics in the prediction of multiple sclerosis?

Lookup NU author(s): Professor James WasonORCiD


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For most of us, the foundations of our understanding of genetics were laid by considering Mendelian diseases in which familial recurrence risks are high, and mutant alleles are both necessary and sufficient. One consequence of this deterministic teaching is that our conceptualization of genetics tends to be dominated by the notion that the genetic aspects of disease are caused by rare alleles exerting large effects. Unfortunately, the preconceptions that flow from this training are frequently erroneous and misleading in the context of common traits, where familial recurrence risks are modest, and for the most part the relevant alleles are neither rare, necessary, nor sufficient. For these common traits, the genetic architecture is far more complex, with susceptibility rather than causality resulting from the combined effects of many alleles, each exerting only a modest effect on risk. None of these alleles is sufficient to cause disease on its own, and none is essential for the development of disease. Furthermore, most are carried by large sections of the population, the vast majority of which does not develop the disease. One consequence of our innate belief in the Mendelian paradigm is that we have an inherent expectation that knowledge about the genetic basis for a disease should allow genetic testing and thereby accurate risk prediction. There is an inevitable feeling that the same should be true in complex disease, but is it? © 2010 American Neurological Association.

Publication metadata

Author(s): Sawcer S, Ban M, Wason J, Dudbridge F

Publication type: Review

Publication status: Published

Journal: Annals of Neurology

Year: 2010

Volume: 67

Issue: 1

Pages: 3-10

Print publication date: 01/01/2010

Online publication date: 09/11/2009

ISSN (print): 0364-5134

ISSN (electronic): 1531-8249


DOI: 10.1002/ana.21911

PubMed id: 20186855