Parent-of-origin effect in multiple sclerosis: observations in half-siblings

Lancet. 2004 May 29;363(9423):1773-4. doi: 10.1016/S0140-6736(04)16304-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mothers*
  • Multiple Sclerosis / genetics*
  • Parents
  • Siblings*