Multiple sclerosis is a complex trait in which occurrence rates in offspring are 20-50-fold greater than in the general population. Parent-of-origin effects have been difficult to screen for, since most cases are sporadic. We have compared recurrence risks in half-siblings with respect to their parent in common. Of the 1567 index cases with half-siblings in multiple sclerosis clinics across Canada, we recorded 3436 half-siblings and 2706 full-siblings. Age-adjusted full-sibling risk was 3·11%. By contrast, half-sibling risk in the same families was significantly lower at 1·89% (χ2 test, p=0·006), but higher than expected if familial risk was simply polygenic. For maternal half-siblings, the risk was 2·35% (34 affected siblings of 1859), and 1·31% for paternal half-siblings (15 of 1577), (p=0·048). The difference in risk suggests a maternal parent-of-origin effect in multiple sclerosis susceptibility.
CITATION STYLE
Ebers, G. C., Sadovnick, A. D., Dyment, D. A., Yee, I. M. L., Willer, C. J., & Risch, N. (2004). Parent-of-origin effect in multiple sclerosis: Observations in half-siblings. Lancet, 363(9423), 1773–1774. https://doi.org/10.1016/S0140-6736(04)16304-6
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