Multiple Sclerosis (MS) is not hereditary. However, as is the case with other autoimmune diseases, it is believed that genetics plays some role in a person developing MS. We look at how big a role that is, what other factors are believed to cause MS, and how putting the pieces together can help advance treatment.
What Causes Multiple Sclerosis?
The short answer is ‘we do not know.’
The slightly longer answer is that there does not seem to be one single cause of MS. Rather, a complex combination of factors each play a role. Aside from genetics, the areas of research that can help put the pieces together are:
- Infectious agents – Studying the role viruses play in the development of MS
- Epidemiology – The study of large population groups and why some regions have higher rates of MS than others
- Immunology – Study of the immune system and what causes it to attack healthy cells
The Role of Genetics in Multiple Sclerosis
As is generally the case with autoimmune diseases, multiple sclerosis is not hereditary. It is not passed down in a predictable fashion like, say, cystic fibrosis is.
The risk of a child developing a disease like cystic fibrosis is quite straight-forward to calculate because it is caused by a mutation to a specific gene. If both parents carry the defective gene, for example, the risk is 25%.
The picture is less clear with MS. Variations (alleles) of over 200 genes have been associated with the condition, yet each only represents a small increase in risk. The more of these variations you have, the more likely you are to develop MS, but no genetic test can accurately predict this likelihood.
Perhaps the most insightful statistic regarding the role of genetics in the development of MS relates to identical twins, who share the same genetic makeup. If one twin lives with MS, there is around a 20%-25% that the other will develop it as well. Were MS purely a genetic disorder, either both or neither would develop it.
Now, compare that to your estimated lifetime risk of developing MS if another family member has it:
- Non-identical twin: 1 in 22
- Another sibling: 1 in 37
- Parent: 1 in 67
- Child: 1 in 48
The lifetime risk in the general population is estimated to be anywhere between 1 in 330 and 1 in 1000 (geographical location goes some way in explaining the large discrepancy in these numbers, which we will get to later).
What we can deduce from this information is that genetic factors clearly play an important role in the development of MS, but do not tell the whole story.
Your genes may determine your underlying susceptibility to MS but something else, it seems, determines whether or not you actually develop the disease.
Learn more about autoimmune diseases with our 3-part series:
- Autoimmune Disease Series: What is Autoimmune Hepatitis?
- Autoimmune Disease Series: What is Autoimmune Encephalitis?
- Autoimmune Disease Series: What is Autoimmune Thyroid Disease?
Are Viruses the Trigger for Multiple Sclerosis?
It has long been theorized that viruses can trigger autoimmune diseases. When it comes to MS, the Epstein-Barr virus (EBV) is among those suspected to do just that, along with other members of the human herpesviruses (including Varicella Zoster virus and human herpesvirus 6).
One train of thought revolves around antigens. Antigens are markers that every cell has. Those produced in your body, called self-antigens, are unique to you. When your body finds foreign antigens, such as from viruses and bacteria, it triggers your immune system to react and fight them.
If EBV antigens are similar to auto-antigens found in parts of your central nervous system, such as the myelin basic protein, it could cause the immune system to mistakenly attack the healthy cells as well as the foreign invaders. This phenomenon is known as ‘molecular mimicry.’
EBV is believed to infect at least 90% of the world’s population but doesn’t usually result in symptoms. Obviously, therefore, infection alone does not cause MS. However, when EBV does lead to symptoms – most commonly in the form of infectious mononucleosis (mono) – it seemingly increases one’s risk of MS.
Interestingly, EBV that leads to mono has been linked to at least six other autoimmune diseases: lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes.
This could help explain why people living with one autoimmune disease are at risk of developing subsequent ones.
Aside from autoimmune diseases, EBV may also cause certain types of cancer, such as Hodgkin lymphoma. For a virus that usually goes unnoticed, EBV can be remarkably sinister. It is also adaptive, goes through different phases throughout its lifecycle, and remains ‘hidden’ within your cells even when it is dormant. In fact, it never leaves your body once you have become infected.
The nature of EBV (and other members of the human herpesvirus family) makes developing a vaccine challenging. Nonetheless, it is an area of significant research, with recent developments offering some cause for optimism.
It is too simplistic to suggest such a vaccine would suddenly prevent MS and the other diseases associated with EBV, but it would help shed light on the exact nature of the virus and its role in the development of autoimmune diseases.
Aside from viruses, epidemiological studies (those that focus on defined populations) suggest there are other factors to consider when it comes to understanding the causes of MS.
Epidemiological Studies: Who Gets MS?
Epidemiological studies help identify patterns in population groups, upon which theories can be formed and tested.
Regarding multiple sclerosis, one of the more curious observations is that it is more prevalent in places farther away from the equator than those close to the equator. Canada, Scotland, and New Zealand, for example, have high prevalence rates.
Not only that, but the onset of symptoms usually occurs at a younger age.
It could be due to the fact that countries close to the equator have greater UVB levels all year round. UVB stimulates the production of vitamin D, which may be protective against MS. It is suspected that vitamin D has a positive effect on the immune system, although the exact nature of the relationship is unknown.
The phenomenon appears to be more pronounced in the western hemisphere, with many countries in northern Europe having higher rates than their eastern counterparts that lie on a similar latitude. Whether this is due to environmental factors, genetics, or a combination of both, remains a mystery.
It is often said that Caucasians are more at risk of MS than any other racial group, which would offer a potential explanation. However, this common wisdom has widely challenged and there is no conclusive evidence that race plays a significant role in one’s likelihood of developing MS.
Lifestyle factors, such as smoking, alcohol, and drug abuse, have been linked to an increased risk MS, while a diet containing fish and/or fish supplements may offer a level of protection. Such lifestyle factors could help explain the geographic disparity in the prevalence of MS.
Another observation made by epidemiological studies is that women are around three times likelier than men to get MS.
The fact that women get MS more than men is not surprising, as it is the case for practically every autoimmune disease. The phenomenon is more pronounced in other diseases. About 90% of lupus cases, for example, are in women.
As a result, it has been suggested that X chromosomes, of which women have two and men have one, play a particularly crucial role in the development of autoimmune diseases. In particular, skewed X chromosome inactivation has been identified as a possible link. In females, one of the X chromosomes is usually randomly inactivated; skewed chromosome inactivation is when one of the X chromosomes is favored in >75% of cells.
It is too complicated to discuss in detail on this post, but this article does an excellent job of describing how skewed X chromosome inactivation may be related to autoimmune disease, while this study is worth reading if you want to get into more detail.
As with the geographical disparity in MS prevalence, however, the theories about why women are more susceptible to autoimmune diseases require further research.
Epidemiology studies tend to generate more questions than they answer. However, the patterns they find often provide the foundation for the various arms of research discussed, which help us gradually understand the deeply complicated mechanisms of MS.
Of course, given that MS is an autoimmune disease, there is another relevant field of research.
Mysteries of the Immune System
Taking all of the above into consideration, it seems likely that genetics, viruses, and environmental factors all contribute to the development of multiple sclerosis. The ways in which they do so are phenomenally complex.
Immunology is the field of research devoted to answering the many mysteries that shroud the immune system.
With autoimmune diseases seemingly on the rise, it is a hugely important field of research.
A greater understanding of what the immune system is actually doing when it attacks the body sheds lights on the underlying mechanisms of diseases like MS. This then provides the foundation for treatments. In recent years, biological treatments, such as TNF inhibitors, and disease-modifying therapies, such as ocrelizumab, go beyond simply treating symptoms and can actually slow the progress of the disease.
Such treatments are helping people with MS maintain a higher quality of living for longer.
Nonetheless, a cure for MS (and other autoimmune diseases) remains elusive. Similarly, there are no effective preventative measures, such as vaccines.
Ultimately, piecing the puzzle of MS together requires research from a diverse range of fields, as discussed in this article. As each piece helps the picture become that bit clearer, the greater the possibilities for treatment and prevention become.
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