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From the Departments of Neurology (O.H.K., B.G.W.) and Health Sciences Research (E.J.A., S.J.A., M.D.), Mayo Clinic College of Medicine, Rochester, MN; Division of Epidemiology (L.F.B., P.P.R.), School of Public Health, University of California, Berkeley; Department of Neurology (L.F.B., R.L., S.L.H.), School of Medicine, University of California at San Francisco; and Division of Research (L.F.B.), Kaiser Permanente, Oakland, CA.
Address correspondence and reprint requests to Dr. Orhun H. Kantarci, Department of Neurology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905; e-mail: kantarci.orhun{at}mayo.edu
Objective: Multiple sclerosis (MS) is approximately twice as common among women as men. If men have greater physiologic resistance to MS, they might theoretically require stronger genetic predisposition than women to overcome this resistance. In this circumstance, men would be expected to transmit the disease more often to their children, a phenomenon known as the Carter effect. The authors evaluated whether the Carter effect is present in MS.
Methods: The authors studied 441 children (45 with definite MS) of an affected father or mother (197 families of interest) from 3598 individuals in 206 multiplex pedigrees. The authors compared transmission of MS from affected men with transmission from affected women.
Results: Fathers with MS transmitted the disease to their children more often (transmitted: 18, not transmitted: 99) than mothers with MS (transmitted: 27, not transmitted: 296) (p = 0.032; OR: 1.99, 95% CI: 1.05, 3.77). Adjusting for both the sex of the affected child and multiple transmissions from a single affected parent, the sex of the affected parent remained as an independent risk factor for transmission of MS to children, fathers transmitting more often than mothers (p = 0.036; OR: 2.21, 95% CI: 1.05, 4.63).
Conclusions: The authors have demonstrated the Carter effect in multiple sclerosis (MS). These observations may be explained by greater genetic loading in men that leads to relative excess paternal vs maternal transmission. Linkage analysis in genetic studies of MS may be more informative if patrilineal transmission were given additional weighting.
Supported by the Mayo Foundation and National MS Society Grant nos. RG-2870-A-2, RG 2899, and NIH grant no. RO1 NS26799-16.
Presented in part at the ECTRIMS meeting, Vienna, Austria, October 6–9, 2004; and ASHG meeting, Toronto, Canada, October 26–30, 2004. This study has been awarded the Founder’s Award for 2005 by the American Academy of Neurology.
Disclosure: The authors report no conflicts of interest.
Received December 21, 2005. Accepted in final form March 21, 2006.
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