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Parental transmission of MS in a population-based Canadian cohort

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.

Address correspondence and reprint requests to Professor George Ebers, Department of Clinical Neurology, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK george.ebers{at}clneuro.ox.ac.uk

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.

Editorial, see page 1202

e-Pub ahead of print on June 27, 2007, at www.neurology.org.

Funded by the Multiple Sclerosis Society of Canada Scientific Research Foundation. B.M. Herrera is funded through a PhD studentship from the UK Multiple Sclerosis Society. Dr. Sadovnick is a Michael Smith Foundation Distinguished Scholar.

Disclosure: The authors report no conflicts of interest.

Received February 1, 2007. Accepted in final form April 13, 2007.

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