Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, including the brain and spinal cord. In MS, the immune system mistakenly attacks the protective myelin sheath around nerve cells, disrupting communication. The development of MS involves a combination of genetic and environmental factors.
The Genetic Component of MS
MS is not inherited in a simple, direct manner like single-gene disorders. Instead, individuals inherit a predisposition or susceptibility to developing MS. This genetic predisposition is not typically tied to direct inheritance from only the mother or only the father. It stems from a combination of genetic factors contributed by both parents and the broader family line. Inheriting these specific genes does not guarantee that someone will develop MS, as other factors also play a role.
Key Genes and Inheritance Patterns
Many genes contribute to the overall risk of MS, a concept known as polygenic inheritance, with each gene having a small effect. The most significant genetic risk factor involves variations in the human leukocyte antigen (HLA) complex, particularly the HLA-DRB115:01 allele. This specific allele is strongly linked to MS and can increase an individual’s risk by about three times.
HLA genes are crucial for the immune system’s ability to distinguish the body’s own cells from foreign invaders. Since HLA genes are inherited from both parents, the genetic risk profile for MS is a blend of contributions from both sides of the family. Despite its strong association with MS, HLA-DRB115:01 is also present in many healthy individuals, underscoring that it is a susceptibility gene and not a determinant of the disease. Other genes, such as IL7R-alpha and IL2R-alpha, which also affect immune system function, have been identified as contributing to MS risk, though their impact is less pronounced.
Environmental Factors and MS Risk
Genetic predisposition alone is not sufficient to cause MS; environmental factors play a role in its development. One environmental risk factor is vitamin D deficiency, with lower levels associated with an increased risk of MS. Insufficient vitamin D levels during pregnancy may also increase the risk of MS in offspring. Living farther from the equator, which means less sun exposure, correlates with a higher incidence of MS.
Infection with the Epstein-Barr virus (EBV) has a strong link to MS risk; one study found a 32-fold increased risk after EBV infection. Smoking is another environmental factor that increases MS risk, with smokers having a 1.5 to 2 times higher likelihood of developing the disease. Childhood and adolescent obesity are also linked to a higher risk of MS, particularly in adolescent girls.
Understanding Your Inherited and Personal Risk
An individual’s overall risk of developing MS is a combination of their genetic predisposition and environmental factors. For the general population, the lifetime risk of developing MS is low, around 0.1% to 0.2%. This risk increases with a family history of the condition.
Having a first-degree relative, such as a parent, sibling, or child, with MS raises the risk to 2% to 5%. For example, the risk for a sibling is about 1 in 37, for a child about 1 in 48, and for a parent about 1 in 67. While these figures represent an increased risk compared to the general population, the absolute risk for most individuals with a family history remains relatively low. Studies of identical twins show that if one twin has MS, the other has about a 31% chance of developing the disease, illustrating that genetics are only one part of the equation.