Is MS Hereditary or Genetic?

Factors other than DNA are at play

Medically reviewed by Smita Patel, DO

The exact cause of multiple sclerosis (MS) remains unknown. While genes—the blueprint for who you are—play a role, MS is not directly inherited, as the disease is not passed predictably down through generations of a family.

Multiple sclerosis is a lifelong disease that develops when a person's immune system malfunctions and attacks healthy nerve tissue within the central nervous system (CNS). The CNS consists of the brain, spinal cord, and optic nerves of the eyes.

This article provides insight into how MS is triggered, likely through a complex interaction between a person's genes and their environment. The impact of sex, age, race, and ethnicity on MS development will also be explored.

Why Isn’t MS Considered an Inherited Condition?

Genes are segments of DNA that contain instructions for how your body is built and functions. They are passed down (inherited) from parents to children.

No single gene or group of genes that, when passed down from parent to child, guarantees that MS develops. As such, MS is not an inheritable condition.

That said, a family history of the disease does increase MS risk (a tendency to develop MS). This indicates that a person's genetic makeup influences MS manifestation.

The following statistical findings support the idea that you can inherit a genetic risk for MS:

• In the general population, a person has an estimated 0.3% chance of developing MS in their lifetime.

• If a person has a biological sibling with MS, their chances of developing MS increase twentyfold, rising from less than 1% to 2% to 4%.

• If a person has a biological parent with MS, their risk of developing MS is approximately 5%. If both parents have MS, the risk increases to 12%.

Perhaps the strongest evidence that genes are not the sole cause of MS but do play a part comes from studies of identical twins (siblings from the same pregnancy who share the same DNA).

Such studies have found that if a person has an identical twin with MS, their chances of getting MS are around 30%, or 1 in 3.

Related: Is Multiple Sclerosis Genetic Testing Available?

The Role Genes Play in MS

The idea that genes influence MS risk is further supported by a large study that examined the DNA of over 47,000 people with MS. Within the study, investigators identified 233 genetic variants, also called polymorphisms, associated with increased MS susceptibility.

Polymorphisms are slight changes in the DNA sequence of genes that may or may not impact how the gene functions or interacts with the environment. Many of the discovered genetic variants were found within the human leukocyte antigen (HLA) genes.

The HLA genes are found on the surface of all cells within the body. They code for proteins that help the immune system identify and prevent harmful substances from entering the body and causing disease.

If HLA genes are altered, your body's immune system may target and attack healthy tissue, mistaking it for a foreign invader. Specifically in MS, a person's immune system misguidedly attacks the fatty sheath surrounding nerve fibers (myelin) within the CNS.

Research also suggests that besides wrongly targeting myelin, altered HLA genes may inappropriately interact with potential MS-triggering environmental factors, namely vitamin D (discussed below).

Related: The Immune System and Multiple Sclerosis (MS)

Other Factors

A person's genes can make them vulnerable to MS. However, exposure to specific environmental or lifestyle factors must be present for the disease to occur.

Four crucial environmental and lifestyle factors linked to an increased MS risk include:

Viral Infection

While no single virus has been identified as the trigger for MS, Epstein-Barr virus (EBV) shows the most substantial evidence. EBV, also known as human herpesvirus-4, is primarily spread through saliva (spit) and infects most people, usually in childhood.

If infected as a teenager or adult, EBV can cause infectious mononucleosis (often referred to as mono), a contagious illness causing extreme tiredness, sore throat, swollen lymph nodes, and fever. While symptoms of mono can be managed, there is no cure for EBV. The virus remains latent (inactive) within your body, even after symptoms disappear.

In genetically susceptible individuals, studies show that mono increases a person's risk of developing MS years later, presumably by driving various abnormal inflammatory responses within the nervous system.

Related: Study Finds EBV as the Leading Cause of MS

Vitamin D Deficiency

Vitamin D is made naturally by the skin when exposed to sunlight and can also be obtained through supplements or select foods, namely fatty fish like trout, salmon, tuna, and mackerel.

Vitamin D deficiency (low levels of the vitamin in a person's body) is associated with an abnormal immune system response and an increased risk of getting MS.

Geography and MS Risk

The role of vitamin D deficiency in increasing MS risk is further supported by the fact that MS is more common in people living in higher latitudes. These locations are farther from the equator and, therefore, receive less direct sunlight.

Unfortunately, no consensus exists on how much vitamin D is needed daily to help prevent MS in susceptible individuals. Large studies examining the safety and benefit of high-dose vitamin D supplementation in MS prevention would be helpful.

Obesity

Obesity—a condition of excessive fat defined by a body mass index (BMI) of 30 or above—in childhood and adolescence increases a person's future risk of MS.

It's unclear exactly how obesity and MS are related, although inflammation is a common pathway.

With obesity, excessive fat tissue produces a pro-inflammatory hormone called leptin. Research suggests leptin may encourage abnormal immune cell behavior in autoimmune diseases like MS.

Interestingly, obesity is also associated with vitamin D deficiency, as fat cells hold onto the vitamin, preventing it from entering the bloodstream.

Smoking

Smoking (including secondhand smoke exposure) increases a person's risk of developing MS by initiating an inflammatory cascade within the body.

Experts suspect that a person's immune system confuses lung antigens (toxic agents within cigarette smoke) for myelin antigens—a phenomenon called cross-reactivity.

Scientists also theorize that toxic substances in cigarette smoke could directly damage nerve cells within the brain and spinal cord, possibly triggering or contributing to MS manifestation.

Learn More: Smoking and Multiple Sclerosis

Who’s at Higher Risk for Developing MS?

Besides genetic and environmental/lifestyle factors, a person's biological sex, age, race, and ethnicity also influence their chances for MS.

Regarding sex, MS is nearly 3 times more common in females than males. While not fully teased out, this finding may be explained by differences in sex hormones (e.g., estrogen) and their influence on the immune system. (The terms female and male here relate to chromosomal, anatomical, and biological characteristics rather than gender identity.)

Age is another crucial determinant. Symptoms of MS usually develop between the ages of 20 and 40, although technically, the disease can occur at any age.

Pediatric MS accounts for 3% to 5% of all MS cases and occurs when symptoms appear in children and adolescents before the age of 18. Late-onset MS accounts for another 5% of MS cases and develops in people over the age of 50.

In terms of race and ethnicity, MS occurs in most ethnic groups but is most common among White people of northern European descent. That said, the detection of MS is increasing among Black people compared to White people.

Learn More: Early Warning Signs of Multiple Sclerosis (MS)

Summary

The precise cause of MS is a mystery, although experts suspect the disease is triggered by a complex interaction between a person's genetic makeup and their environment.

Regarding genetics, you cannot directly inherit MS. Still, you can inherit the genetic risk for MS. This means that having a family history of MS increases your chances of developing it.

Various environmental factors are associated with MS development, namely the Epstein-Barr viral infection, a vitamin D deficiency, having obesity in childhood or adolescence, and smoking.

Non-modifiable factors like age, sex, race, and ethnicity also contribute to a person's likelihood of developing MS. The disease is most common in young adults, females, and White people of northern European descent.

Read the original article on Verywell Health.