Parent-of-origin effect in multiple sclerosis

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Abstract
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. Neurology (R) 2009; 73: 602-605