Multiple Sclerosis (MS)


There are several risk factors known to increase the risk of developing multiple sclerosis (MS). These multiple sclerosis risk factors are age, gender, genetics, certain viral infections, ethnicity, climate, vitamin D, other autoimmune diseases, diet, obesity, gut microbiota, smoking, and air pollution.1,2,3

MS and Age

People of any age can be affected by multiple sclerosis, but the disease is more commonly diagnosed among people aged 20 to 40 years.1

MS and Gender

Women have a high risk of developing the relapsing-remitting form of MS, especially at a younger age. The exact cause of this is not well-understood. It could be the result of complex interactions between immunological responses to infections, direct effects of gender or other hormones, or other unknown factors.3 

MS and Genetics

Although MS is not a genetic disease, people with a family history of the disease are more likely to develop it. This suggests there may be genetic factors predisposing people to develop MS.

The main susceptibility allele to MS is a human leukocyte antigen (HLA) Class II gene. Homozygous carriers of the HLA-DRB1*1501 alleles have a 6-fold increase in the risk of developing MS.4

Recent research has shown there may be more than 200 non-HLA single nucleotide polymorphisms near genes involved in adaptive or innate immunity that also increase the risk of MS.5

MS and Viral Infections

Research has shown that certain viruses such as Epstein-Barr virus and human herpesvirus-6, increase the risk of developing MS. However, the exact mechanism of this association is not well-understood. 

It is thought that the Epstein-Barr virus alters gene expression in infected astrocytes, microglia, and B cells, triggering an immune response.3

MS and Ethnicity

Multiple sclerosis is more common among people of Caucasian descent, especially those from Northern Europe. People of Asian, African, or Native American origin have the lowest risk. However, differences in diagnostic criteria, access to magnetic resonance imaging (MRI), life expectancy, and differences in access to health care among different populations could influence the accuracy of prevalence data.6

MS and Climate

Living in a temperate climate seems to increase the risk of developing MS, and the disease is more common among people living in Canada, the northern United States, New Zealand, the southeast of Australia, and Europe than in other areas.1

MS and Vitamin D

Research suggests that low serum levels of vitamin D and low sun exposure increase the risk of MS. In fact, MS prevalence increases with increasing distance from the equator. A higher latitude and a lower sun exposure in adolescence have been linked to a younger age of MS onset.7

ms risk factors
Risk factors for multiple sclerosis. The destruction of the myelin sheath on the axon. Damaged myelin. World Multiple Sclerosis Day. Infographics. Vector illustration on isolated background

MS and Other Autoimmune Diseases

Autoimmune disease such as systemic lupus erythematosus, thyroid disease, pernicious anemia, psoriasis, type 1 diabetes, and inflammatory bowel disease commonly co-occur with MS.1,2

MS and Diet

Although the link between diet and the risk of developing MS is not clear, some studies suggest that polyunsaturated fatty acid intake may reduce the risk of MS.8

MS and Obesity

Research has shown that childhood obesity or obesity in adolescence is associated with the risk of developing MS, especially in females.9 

MS and Gut Microbiota

Microbial imbalance in the gut microbiota has been linked to an increased risk of MS. It is thought that altered microbiota may increase the risk of MS by acting on the immune system.10 Factors modulating gut microbiota include diet, obesity, antibiotic use, and smoking.

MS and Smoking

People who smoke have a greater risk of developing relapsing-remitting MS after an initial clinically isolated syndrome episode. There is a clear dose-response relationship between smoking and MS onset. Quitting smoking is associated with a gradual decline in the increased risk of developing MS, to no increase at 10 years after quitting.11

MS and Air Pollution

Although it is not clear whether air pollution increases the risk of MS, research has shown that there is a strong association between air pollution and having pediatric MS. This could be due to exposure to sulfur dioxide, PM2.5, carbon monoxide, and lead.12 Exposure to air pollution may trigger an inflammatory response in the lungs and the subsequent release of inflammatory cytokines that could be linked to multiple sclerosis.

References

  1. Multiple sclerosis. Mayo Clinic. Accessed May 21, 2021.
  2. Risk factors for multiple sclerosis (MS). Beth Israel Lahey Health Winchester Hospital. Accessed May 21, 2021. 
  3. Waubant E, Lucas R, Mowry E, et al. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol. 2019;6(9):1905-1922. doi:10.1002/acn3.50862
  4. George MF, Briggs FBS, Shao X, et al. Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies. Neurol Genet. 2016;4;2(4):e87. doi:10.1212/NXG.0000000000000087
  5. International Multiple Sclerosis Genetics Consortium. Low-frequency and rare-coding variation contributes to multiple sclerosis risk. Cell. 2018;29;175(6):1679-1687.e7. doi:10.1016/j.cell.2018.09.049
  6. O’Gorman C, Lucas R, Taylor B. Environmental risk factors for multiple sclerosis: a review with a focus on molecular mechanisms. Int J Mol Sci. 2012;13(9):11718-11752. doi:10.3390/ijms130911718
  7. Sintzel MB, Rametta M, Reder AT. Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther. 2018;7(1):59-85. doi:10.1007/s40120-017-0086-4
  8. Bjørnevik K, Chitnis T, Ascherio A, Munger KL, et al. Polyunsaturated fatty acids and the risk of multiple sclerosis. Mult Scler. 2017;23(14):1830-1838. doi:10.1177/1352458517691150
  9. Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology. 2013;5;80(6):548-552. doi:10.1212/WNL.0b013e31828154f3
  10. Cantarel BL, Waubant E, Chehoud C, et al. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med. 2015;63(5):729-734. doi:10.1097/JIM.0000000000000192
  11. Hedström AK, Hillert J, Olsson T, Alfredsson L. Smoking and multiple sclerosis susceptibility. Eur J Epidemiol. 2013;28(11):867-874. doi: 10.1007/s10654-013-9853-4
  12. Lavery AM, Waubant E, Casper C, et al. Urban air quality and associations with pediatric multiple sclerosis. Ann Clin Transl Neurol. 2018;5(10):1146-1153. doi:10.1002/acn3.616

Reviewed by Michael Sapko, MD on 7/1/2021

Reviewed by Michael Sapko, MD, on 7/2/2021.