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From the Wellcome Trust Centre for Human Genetics (B.M.H., S.V.R., S.O., M.J.C., G.C.E.), Oxford University; Department of Clinical Neurology (B.M.H., S.V.R., S.O., M.J.C., G.C.E.), Radcliffe Infirmary, Oxford, UK; and Department of Medical Genetics (I.M.Y., A.D.S.), University of British Columbia, Vancouver, Canada.
* To whom correspondence should be addressed. E-mail: george.ebers{at}clneuro.ox.ac.uk.
Abstract Objective: Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. The precise nature of these factors and mode of inheritance remains unknown. A female predominance is universally found. Recently, offspring of affected fathers were reported to be more likely to have MS than those of affected mothers. This was attributed to the Carter effect, which is seen in polygenic disorders. The Carter effect predicts that affected parents of the sex lesser affected by a disease/trait are more genetically loaded for risk alleles and thus transmit these more often to their offspring. This hypothesis was tested in a population-based Canadian MS cohort. Methods: Using the longitudinal Canadian database, we identified 3,088 nuclear families with one affected parent and a total of 8,401 offspring, of which 798 had MS. Transmission to daughters and sons from affected mothers and fathers was compared. Results: There was equal transmission of MS from affected fathers vs affected mothers (9.41% vs 9.76%). Stratifying by gender of affected parent there were no differences in the female:male sex ratio of affected (2.46% vs 2.41%, p = 0.88) or unaffected offspring (0.91% vs 0.95%, p = 0.46). Conclusions: We observed1 equal disease transmission to offspring from affected mothers and affected fathers,2 no difference in the female:male sex ratio of affected offspring, and previously3 no difference in sibling recurrence risk by gender of parent affected. These findings show no evidence for the Carter effect and do not support the hypothesis of polygenic inheritance of multiple sclerosis susceptibility by parent.
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