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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.
Address correspondence and reprint requests to Professor George C. Ebers, University Department of Clinical Neurology, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK 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.
Abbreviations: CCPGSMS = Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis; MS = multiple sclerosis.
e-Pub ahead of print on June 10, 2009, at www.neurology.org.
*Members of the Canadian Collaborative Study Group are listed in the appendix.
Supported by the Multiple Sclerosis Society of Canada Scientific Research Foundation. S.V.R. is funded by the Medical Research Council of the United Kingdom. G.C.E. is the Action Research Professor of Clinical Neurology at the University of Oxford.
Disclosure: Author disclosures are provided at the end of the article.
Received March 11, 2009. Accepted in final form May 7, 2009.
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