MS Risk Isn't All in the Family

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MS Risk Isn't All in the FamilyBy Neil Osterweil, Senior Associate Editor, MedPage TodayReviewed by Jasmer, MD; Assistant Professor of Medicine, University of California, San FranciscoAugust 22, 2005Also covered by: MSNhttp://www.medpagetoday.com/Neurology/MultipleSclerosis/tb1/1579ReviewVANCOUVER, B.C.-Although some researchers suggest that first-born children and others high up in the birth-order are at greater risk for multiple sclerosis (MS), a large Canadian study suggests that it just isn't so.A study of nearly 11,000 people with MS and their healthy siblings found no relationship between birth order and MS risk, A. Dessa Sadovnick, Ph.D., of the University of British Columbia and colleagues in the Canadian Collaborative Study Group reported in the Aug. 22 online version of Lancet Neurology.In fact, in large family groups the siblings with MS tended to be farther down the birth ladder, according to the researchers.Some MS researchers speculate that the risk for developing MS is greater among children in small families and those who are higher up in the birth order, and that this risk might be due to a "hygiene hypothesis" similar to the model proposed for the development of asthma and atopic dermatitis.The thinking is that older children may be exposed to some as yet unidentified infectious agent such as a virus that could cause MS, whereas their siblings farther down in the birth order are encountering the same infection when their immune systems are younger, more balanced, and more highly primed to evoke an effective protective response, noted Dr. Sadovnick and colleagues."Despite strong evidence against non-genetic familial transmissibility of MS, other research, typically cross-sectional studies of viral antibody concentrations, suggested various infections are involved," Dr. Sadovnick and colleagues wrote. "Reports of direct isolation of infectious organisms have not been replicated. Attention continues to be given to the timing of infection, previously recognized as an important factor in paralysis in polio."Although birth-order studies of MS risk until now have been negative, it's possible that they weren't large enough to detect an effect, the investigators noted. To better address the question, they looked at data from the Canadian Collaborative Project on Genetic Susceptibility to MS.The study included 10,995 people with MS and 26,336 healthy siblings. The data were grouped according to whether one or more siblings in a group had MS. Sibships, or the number of siblings in addition to the index case, ranged from one to 19.The investigators compared the mean ages of siblings both with and without MS, stratified by sibling group size, to determine whether an association between MS and age could be a confounding factor in determining the relationship between birth order and disease.They also calculated the expected birth order, controlling for sibship size, and compared this with the actual observed birth order.In the analysis of the overall data, they found no association between birth order and MS risk. In fact, in families where the individuals with MS had at least seven siblings, the index cases occurred later in the birth order than expected, in direct contrast to what would be expected if the hygiene hypothesis were correct.Regardless of the sibling group size or whether there were one of more siblings per family with MS, the MS patients were younger than those who were unaffected by about one to two years.Although the study debunks the notion of birth order as a predictor of MS, it does not rule out other environmental factors, Dr. Sadovnick and colleagues commented."The data presented here cast no doubt on the importance of environmental factors to MS risk, and suggest that environmental risks for MS must be accounted for by factors that do not affect birth-order position," the authors wrote. "In combination with extensive data from half-siblings, adoptees, conjugal pairs, step-siblings, and consanguineous matings, birth-order studies suggest that environmental effects in MS act on susceptible hosts at a broad population level."Primary source: The Lancet NeurologySource reference:DOI:10.1016/S1474-4422(05) 70170-8.