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Published online before print June 10, 2009, doi:10.1212/WNL.0b013e3181af33cf)
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Received March 11, 2009
Accepted May 7, 2009

Parent-of-origin effect in multiple sclerosis. Observations from interracial matings

S. V. Ramagopalan DPhil, I. M. Yee MSc, D. A. Dyment MD, DPhil, S.-M. Orton DPhil, R. A. Marrie MD, PhD, FRCPC, A. D. Sadovnick PhD, G. C. Ebers MD, FRCP, FRCPC, FMedSci*, For the Canadian Collaborative Study Group

From the Wellcome Trust Centre for Human Genetics (S.V.R., D.A.D., S.-M.O., G.C.E.), University of Oxford, Headington; Department of Clinical Neurology (S.V.R., D.A.D., S.-M.O., G.C.E.), University of Oxford, John Radcliffe Hospital, Oxford, UK; Department of Medical Genetics (I.M.Y.) and Faculty of Medicine (A.D.S.), Division of Neurology, University of British Columbia, VCHA-UBC Hospital, Vancouver; and University of Manitoba Health Sciences Centre (R.A.M.), Winnipeg, Canada.


* To whom correspondence should be addressed. E-mail: george.ebers{at}clneuro.ox.ac.uk.

Background: Multiple sclerosis (MS) is a complex neurologic disease with a striking geographical distribution. In Canada, prevalence is high in Caucasians of Northern European ancestry and uncommon in North American Aboriginals, many of whom now have Caucasian admixture.

Methods: The population-based Canadian Collaborative Project on the Genetic Susceptibility to MS provided the characteristics of 58 individuals with 1 Caucasian and 1 North American Aboriginal parent from a database of 30,000 MS index cases.

Results: We found that MS index cases with a Caucasian mother and a North American Aboriginal father had a higher sib recurrence risk and greater F:M sex ratio (p = 0.043) than patients with a North American Aboriginal mother and Caucasian father.

Conclusions: Maternal parent-of-origin effects in multiple sclerosis disease etiology previously seen in studies of half-siblings and avuncular pairs are also seen in Caucasian-North American Aboriginal admixture matings and warrant further investigation. A differential influence of maternal risk transmission on the sex ratio of affected offspring is implied. The method of analysis used may have broader implications for detection of parent-of-origin effects in admixture cohorts.


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Multiple sclerosis: Evidence of maternal effects and an increasing incidence in women
John W. Rose
Neurology 2009 73: 578-579. [Full Text] [PDF]



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J. W. Rose
Multiple sclerosis: Evidence of maternal effects and an increasing incidence in women
Neurology, August 25, 2009; 73(8): 578 - 579.
[Full Text] [PDF]


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