S.V. Ramagopalan, DPhil, of the Wellcome Trust Centre for Human Genetics at the University of Oxford, UK, and colleagues examined 30,000 MS cases from the Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) and identified 58 individuals with one Caucasian parent and one North American Aboriginal parent. Of these, 27 had a Caucasian mother and 31 had a North American Aboriginal mother. Although the total number of affected offspring was similar in the two mating types studied, the sex ratio differed. Female-to-male sex ratio was 7:1 for patients with MS who had a Caucasian mother, compared with a 2:1 ratio for those with a Caucasian father.
“A parent-of-origin effect (maternal) has been repeatedly observed in MS, based on studies of half-siblings, sibships including dizygotic twins, a large extended Dutch pedigree, and avuncular pairs, as well as timing of birth effect,” the study authors noted. “The comparison of offspring from interracial matings is a novel method of analysis to look for parent of origin effects.
“The data from this study hint at an intriguing possibility that the observed female preponderance of MS could result from environmental factors acting upon mothers to differentially affect MS risk more in female than in male offspring,” the researchers pointed out.
In a related editorial, John W. Rose, MD, commented that this study “illustrated the continued potential of the CCPGSMS to address interesting questions related to the disease.… By evaluating a small set of MS patients with a Caucasian parent and a Native Aboriginal American parent, the investigators were able to assess parental effects on the disease,” he continued. “The susceptibility to disease is presumed to be predominantly introduced by the Caucasian parent based on previous investigations. In this admixture study, the results demonstrate a maternal effect which strongly influences the sex ratio of offspring affected by MS, linking these two classes of gender differences in MS.”
Ramagopalan SV, Yee IM, Dyment DA, et al. Parent-of-origin effect in multiple sclerosis: observations from interracial matings. Neurology. 2009;73(8):602-605.
Rose JW. Multiple sclerosis: evidence of maternal effects and an increasing incidence in women. Neurology. 2009;73(8):578-579.