Parent-of-origin effect in multiple sclerosis: observations in half-siblings.
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.
Ebers
G C
GC
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. george.ebers@clinical-neurology.oxford.ac.uk
Sadovnick
A D
AD
Dyment
D A
DA
Yee
I M L
IM
Willer
C J
CJ
Risch
Neil
N
D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009035:Mothers; D009103:Multiple Sclerosis / Q000235:genetics*; D010290:Parents; D035781:Siblings