Multiple Sclerosis Risk

Last Updated: November 3, 2021

Multiple sclerosis affects 2–140 people per 100,000. Although the exact cause of MS is unknown, factors such as sex, geographical location, and environmental factors can help predict one’s risk of developing the condition.

research-feedResearch feed
Summary

The immune system is heavily involved in the pathophysiology (changes brought on by disease) of MS, but it’s not clear what provokes this response in the first place. Viral infections, genetics, and environmental factors have all been connected to MS in observational research. Extreme grief may also predispose people to the disease.[1] [2][3][4]

Autoimmunity

The high degree of immune involvement in MS and the fact that women are more prone to autoimmune diseases (and to MS) than men strongly suggests that MS is an autoimmune condition. This hasn’t been directly proven though; ideally, researchers would be able to identify a single self-antigen or autoreactive T cell that could cause disease in otherwise healthy lab animals.[5] Although this has been possible with certain autoimmune diseases, such as myasthenia gravis and lupus, it is a very high standard, and it may be a long time before this can be done for MS.[6]

Viral infections

It’s possible that a viral infection sets MS into motion.[2] People who have Epstein-Barr virus antibodies in their blood (which suggests being previously infected with the virus) have about 4.5 times greater odds of developing MS than those who have not had the virus. Similarly, people with a history of infectious mononucleosis (typically caused by the Epstein-Barr virus) have about 2 times greater odds of developing MS than people who haven’t had mono.[4] It’s worth noting, however, that about 90% of the world’s population tests positive for Epstein-Barr by age 35.[7] If a risk factor is common, it’s easy to correlate it with many things (e.g., “drinking water” could be a risk factor for many diseases, because everyone with a given disease is likely to have drunk water).

Genetics

There aren’t any single alleles (gene variations) known to cause MS. That being said, certain alleles in the genes that encode for human leukocyte antigens (HLAs) in the major histocompatibility complex (MHC, part of the genome that encodes for a variety of cell surface proteins that are used by the immune system to identify “self”) are associated with a considerable increase in risk of MS.[8] Additionally, a number of genes outside the MHC are associated with small increases or decreases in risk. Individuals who have a first-degree family member with MS have an increased risk of developing the condition compared with people who have no immediate family history of MS. In a study conducted in Denmark, for example, first-degree relatives of someone with MS had about a 7 times increased risk of developing it over their lifetime.[9] Interestingly, spouses did not have any increased risk; the authors suggest that this rules out environmental factors, but it’s probably more correct to say that without certain genetic factors present, environmental factors aren’t likely to have a strong effect on whether the disease manifests.

Sex

Women have an increased risk of developing MS compared with men, a relative risk that has been increasing. Currently, women are at about 3 times the risk of developing MS as men.[10][11] It’s not clear why this is, but some speculations include:

  • Women are having children less often and later in life; previous pregnancy and number of children have both been associated with a lower risk of MS in observational research.[12]
  • Women have much stronger T helper 1 (Th1) immune responses than men. Given that MS is characterized by a high level of Th1 activation, it’s possible that women’s predisposition for MS is due to a sex-specific difference in immune system activity.[13]

Behavior/Environment

Vitamin D

There is some observational evidence that vitamin D protects against the development and progression of MS, as well as MS-related disability [14][15]. High serum levels of vitamin D are associated with a lower risk of MS, and both supplemental vitamin D and sun exposure (which increases vitamin D) show the same trend. Furthermore, a Mendelian randomization trial found that, as the number of alleles associated with low vitamin D in four genes increases, so does the risk of MS.[16] Many of the studies that evaluate vitamin D have a high risk of bias, however, and shouldn’t be considered strong evidence of this relationship.[4]

An important caveat to these findings is that a large amount of this research has been conducted in predominantly white countries, such as Australia and the Scandinavian countries. A study in the U.S. found that, among non-Hispanic white people, higher serum levels of vitamin D were associated with a lower risk of developing MS, but this relationship wasn’t present in the Black or Hispanic study participants. [17] Given that the degree of skin pigmentation is associated with lower levels of vitamin D, this weakens the evidence that vitamin D is somehow a cause of MS in all people. Additionally, supplementing with vitamin D in people with MS hasn’t seemed to improve the condition in clinical trials.[18]

Obesity

Individuals who are obese in early life ( childhood to young adulthood) have about double the risk of developing MS as individuals who are not obese during this time period.[14][19]

Smoking

There is strong observational evidence that smoking increases the risk of MS by 20–60%, depending on the amount someone smokes. It’s possible that this increase in risk is related to the vascular or immune effects of smoking, and/or the general toxicity of compounds found in cigarette smoke. [15][4]

Geographic Location

The prevalence of MS varies considerably across countries: regions in North America and Europe can have a prevalence of over 100 cases per 100,000 people, while regions in East Asia and sub-Saharan Africa have approximately 2 per 100,000 people.[20]

Don't miss out on the latest research

References
  1. ^J Li, C Johansen, H Brønnum-Hansen, E Stenager, N Koch-Henriksen, J OlsenThe risk of multiple sclerosis in bereaved parents: A nationwide cohort study in DenmarkNeurology.(2004 Mar 9)
  2. ^Rachael E Tarlinton, Ekaterina Martynova, Albert A Rizvanov, Svetlana Khaiboullina, Subhash VermaRole of Viruses in the Pathogenesis of Multiple SclerosisViruses.(2020 Jun 13)
  3. ^D Kotzamani, T Panou, V Mastorodemos, M Tzagournissakis, H Nikolakaki, C Spanaki, A PlaitakisRising incidence of multiple sclerosis in females associated with urbanizationNeurology.(2012 May 29)
  4. ^Lazaros Belbasis, Vanesa Bellou, Evangelos Evangelou, John P A Ioannidis, Ioanna TzoulakiEnvironmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analysesLancet Neurol.(2015 Mar)
  5. ^Abhijit Chaudhuri, Peter O BehanMultiple sclerosis is not an autoimmune diseaseArch Neurol.(2004 Oct)
  6. ^E S RoachIs multiple sclerosis an autoimmune disorder?Arch Neurol.(2004 Oct)
  7. ^Katherine Luzuriaga, John L SullivanInfectious mononucleosisN Engl J Med.(2010 May 27)
  8. ^Stephen Sawcer, Robin J M Franklin, Maria BanMultiple sclerosis geneticsLancet Neurol.(2014 Jul)
  9. ^Nete Munk Nielsen, Tine Westergaard, Klaus Rostgaard, Morten Frisch, Henrik Hjalgrim, Jan Wohlfahrt, Nils Koch-Henriksen, Mads MelbyeFamilial risk of multiple sclerosis: a nationwide cohort studyAm J Epidemiol.(2005 Oct 15)
  10. ^Nils Koch-Henriksen, Per Soelberg SørensenThe changing demographic pattern of multiple sclerosis epidemiologyLancet Neurol.(2010 May)
  11. ^Shannon E Dunn, Lawrence SteinmanThe gender gap in multiple sclerosis: intersection of science and societyJAMA Neurol.(2013 May)
  12. ^A-L Ponsonby, R M Lucas, I A van der Mei, K Dear, P C Valery, M P Pender, B V Taylor, T J Kilpatrick, A Coulthard, C Chapman, D Williams, A J McMichael, T DwyerOffspring number, pregnancy, and risk of a first clinical demyelinating event: the AusImmune StudyNeurology.(2012 Mar 20)
  13. ^Monan Angela Zhang, Dorothy Rego, Marina Moshkova, Hania Kebir, Andrzej Chruscinski, Hoangkim Nguyen, Rainer Akkermann, Frank Z Stanczyk, Alexandre Prat, Lawrence Steinman, Shannon E DunnPeroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific wayProc Natl Acad Sci U S A.(2012 Jun 12)
  14. ^Alberto Ascherio, Kassandra L MungerEpidemiology of Multiple Sclerosis: From Risk Factors to Prevention-An UpdateSemin Neurol.(2016 Apr)
  15. ^Mahmood Moosazadeh, Fatemeh Nabinezhad-Male, Mahdi Afshari, Mohammad Mehdi Nasehi, Mohammad Shabani, Motahareh Kheradmand, Iraj AghaeiVitamin D status and disability among patients with multiple sclerosis: a systematic review and meta-analysisAIMS Neurosci.(2021 Feb 5)
  16. ^Lauren E Mokry, Stephanie Ross, Omar S Ahmad, Vincenzo Forgetta, George Davey Smith, David Goltzman, Aaron Leong, Celia M T Greenwood, George Thanassoulis, J Brent RichardsVitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization StudyPLoS Med.(2015 Aug 25)
  17. ^Kassandra L Munger, Lynn I Levin, Bruce W Hollis, Noel S Howard, Alberto AscherioSerum 25-hydroxyvitamin D levels and risk of multiple sclerosisJAMA.(2006 Dec 20)
  18. ^Xiaofan Yuan, Lei Guo, Chuan Jiang, Xu Yang, Jie HuangThe Effect of Different Administration Time and Dosage of Vitamin D Supplementation in Patients with Multiple Sclerosis: A Meta-Analysis of Randomized Controlled TrialsNeuroimmunomodulation.(2021 Jul 2)
  19. ^Lauren E Mokry, Stephanie Ross, Nicholas J Timpson, Stephen Sawcer, George Davey Smith, J Brent RichardsObesity and Multiple Sclerosis: A Mendelian Randomization StudyPLoS Med.(2016 Jun 28)
  20. ^E Leray, T Moreau, A Fromont, G EdanEpidemiology of multiple sclerosisRev Neurol (Paris).(2016 Jan)