Lancet. 2004 May 29;363(9423):1773-4
Ebers GC, Sadovnick AD, Dyment DA, Yee IM, Willer CJ, Risch N.
The Wellcome Trust Centre for Human Genetics, University of Oxford,
Oxford, UK
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% (chi2 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.