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Is MS hereditary?

Is MS hereditary? We know that MS is more common in family members of people with MS. Some authorities say it is up to eighty times more common in first degree relatives like brothers and sisters or children of a person with MS. We now know that identical twins have 300 times the risk of other people of getting MS if the other twin has the disease. It has long been taught that if you have 10 pairs of identical twins in which one of each pair gets MS, then three of the other twins will get the disease, that is a 30% risk.

A very large Danish study in 2005 clarified this further.1 This study of 13,286 people with MS showed that amongst identical twins the risk was 24%, and for non-identical twins the risk was 3%. A first degree relative such as the son of a mother with MS, has 20-40 times the risk of getting the disease than someone without such a relative.2
So to work out actual incidence figures for a particular case, you need to know the incidence of MS in that place. This varies enormously between populations. For instance in far north Queensland, Australia, the incidence is 10 cases of MS per 100,000 people in the population. If you are the first degree relative of someone in that population then you have 20-40 times that risk, that is 200-400 per 100,000 population, that is 2-4 per thousand or 0.2% to 0.4%. If you live in some parts of Canada, where the incidence can be as high as 500 cases of MS per 100,000 people, and you are the first degree relative of someone with MS then you have 20-40 times that risk, that is 10,000-20,000 per 100,000, or 1 in 10 to 1 in 5, that is an incidence of 10-20%. The incidence in Australia varies enormously from about 10 per 100,000 in far north Queensland to as much as 100 per 100,000 in parts of Tasmania, so the actual risk to relatives of those with MS varies ten-fold as per the calculation above. It is also important to note that this risk increases with the number of relatives a person has with MS, and of course with environmental factors such as smoking, which doubles the risk.

There has now been a very substantial research effort expanding our knowledge in this area from Canada. The Canadian Collaborative Study Group has looked at the question is multiple sclerosis hereditary over many years, and has published a number of papers on various aspects of the family risks of getting MS. Initial studies published in 1995 showed that the increased risk of MS in family was due to genetic factors, that is factors passed from parent to child, not factors in the shared family environment.3 The researchers screened 15,000 people with MS with questionnaires, and compared the risk of MS in genetically related family members to that in family members who had been adopted, and therefore were not genetically related. Adopted family members had no higher risk than the general population of getting MS. This is reassuring for people who may worry about ‘catching’ MS by living with someone with MS. It is clear that this does not happen.
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More recently the same group in Canada has examined the question is MS genetic by evaluating MS risk in 687 stepsiblings of 19,746 MS index cases. This was to determine whether any transmissible factor in a family’s micro-environment might enable one to ‘catch’ MS.4 They found the risk of MS in these stepsiblings to be indistinguishable from that of the general population. So it is clear now that there is no transmissibility other than genetic from one affected individual to another in this high MS prevalence area of Canada. So environment influences MS risk at a population level, not a family level.

The step-sibling research suggested that the majority of the risk comes from the mother having MS, at approximately twice the risk of getting MS as if the father has MS.5 This has been contradicted by US research showing that men with MS pass the disease on twice as often to their children as women.6 The situation is unclear at present. A follow up study of the actual genes involved in determining susceptibility to MS showed that, as expected, MS is not inherited as a result of a single gene, like diseases such as cystic fibrosis or muscular dystrophy.7 The susceptibility to MS is the result of the interaction of several genes (credit cassidy here). Hence predicting its occurrence in offspring is not possible at present.

A key area of interest for many people is estimating the increased risk of getting MS that a brother or sister of someone with the disease has. The Canadian Group has shown that the risk is higher if a parent also has or had MS, if the disease occurred at an earlier age, and if the sibling for whom we are estimating the risk of MS is female.8 Depending on background risk in the population in question (for instance that risk is higher in Canada than in Australia), the combination of factors above (a woman with a parent developing the disease at a young age for example), and such things as whether the person smokes and has a low vitamin D level, this risk may be as high as 1 in 5 or 1 in 10. For more details on exact risks, see the book Overcoming Multiple Sclerosis. So, is MS hereditary? Well, yes to some extent, but the good news is that the risk may be very substantially reduced. For what to do about the risk, see the webpage on Preventing MS in Family Members.
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  1. Hansen T, Skytthe A, Stenager E, et al. Concordance for multiple sclerosis in Danish twins: an update of a nationwide study. Mult Scler 2005; 11:504-510
  2. Sadovnick AD, Ebers GC, Dyment DA, et al. Evidence for genetic basis of multiple sclerosis. The Canadian Collaborative Study Group. Lancet 1996; 347:1728-1730.
  3. Ebers GC, Sadovnick AD, Risch NJ. A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 1995; 377:150-151.
  4. Dyment DA, Yee IM, Ebers GC, et al. Multiple sclerosis in stepsiblings: recurrence risk and ascertainment. J Neurol Neurosurg Psychiatry 2006; 77:258-259
  5. Ebers GC, Sadovnick AD, Dyment DA, et al. Parent-of-origin effect in multiple sclerosis: observations in half-siblings. Lancet 2004; 363:1773-1774
  6. Kantarci OH, Barcellos LF, Atkinson EJ, et al. Men transmit MS more often to their children vs women: the Carter effect. Neurology 2006; 67:305-310
  7. Ebers GC, Kukay K, Bulman DE, et al. A full genome search in multiple sclerosis. Nat Genet 1996; 13:472-476.
  8. Sadovnick AD, Yee IM, Ebers GC, et al. Effect of age at onset and parental disease status on sibling risks for MS. Neurology 1998; 50:719-723.