Chronic Fatigue Syndrome Genetics

It's likely not inherited, but genes play a role

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can run in families. That has led researchers to ask whether it is a hereditary disease, or one that can be passed down from one person to another.

So far, research doesn't support this. But your genes can make you more likely to develop ME/CFS under certain conditions—what's called a genetic predisposition.

This article explains what a genetic predisposition to ME/CFS means for you. You'll also learn about familial patterns , what other factors contribute to the condition, and how genetic research is aiming to shape how chronic fatigue syndrome is diagnosed and treated.

Several generations of a multi-ethnic family stand in front of a house.

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Genetic Predisposition and ME/CFS Risk

Inheriting a genetic predisposition to ME/CFS doesn’t mean you’ll someday develop it. A predisposition is different from a hereditary disease.

  • True genetic disease: If you inherit the gene, you either have or will eventually have the disease.
  • Genetic predisposition: You inherit genes that make it possible or likely for you to develop the condition under the right circumstances. If those circumstances never come to pass, you probably won’t develop the condition.

Research suggests you only inherit about 10% of the overall causes of ME/CFS. This suggests genetic factors combine with environmental factors to cause the condition.

Patterns in Families

In a study looking at first, second, and third-degree relatives of people with ME/CFS, data suggest that risk is still notable for the more distant relatives.

 Type of Relative Who That Is Increase in ME/CFS Risk
1st degree Parent, sibling, child 2.7 times
2nd degree Grandparent, grandchild, aunt/uncle, niece/nephew, half-sibling 2.34 times
3rd degree First cousin, great grandparent, great grandchild 1.93 times

It’s unlikely that there’s one “ME/CFS gene,” though. Studies show the pattern of cases within families doesn’t follow a predictable pattern like some diseases do.

Recap

Genetics plus environmental triggers are believed to cause ME/CFS. It runs in families, but not in the predictable patterns of a truly inherited disease. Having a relative with ME/CFS means you are at greater risk for it, not that you will definitely go on to develop it.

Genes Associated With ME/CFS

Researchers have identified dozens of genes that may be involved in ME/CFS. Studies have found changes in genes dealing with:

  • Structure of the blood-brain barrier, what's essentially a gatekeeper that keeps potentially harmful things (like bacteria or toxins) from crossing from the bloodstream and into the brain
  • The brain's ability to learn and make new connections (neuroplasticity)
  • Immune-system activation not related to infection
  • Regulation of the immune system
  • Metabolic function, including sugar and fat processing
  • Hormone activity (naturally produced glucocorticoids, estrogen, androgens)
  • Receptors of glutamate, a brain chemical known as a neurotransmitter
  • Sensitivity to glucocorticoids, natural steroid hormones
  • Stress-response system regulation
  • Enzymes that affect DNA expression (the instructions in your DNA becoming a reality)
  • Functioning of T cells, a type of immune cell

One study found more than 100 changes to genes related to T cells alone. Some immune-system changes may even be an underlying mechanism of ME/CFS.

Infections As Triggers

According to 2018 research, certain infections may cause B cells in people who are genetically susceptible to ME/CFS to become autoreactive.

B cells are a part of the immune system that creates proteins called antibodies. These cells are essential, as they help fight infections like viruses. However, when they turn autoreactive, they start producing autoantibodies—proteins that attack healthy tissues as though they are a dangerous invader.

In ME/CFS, autoantibodies appear to target key enzymes dealing with energy metabolism. Researchers believe that may be the cause of ME/CFS's hallmark symptom: post-exertional malaise, or the worsening of symptoms after expending little mental or physical energy.

The Epstein-Barr virus (EBV), which causes mononucleosis, is believed to contribute to ME/CFS development. In susceptible people, it appears to cause abnormal activity from B cells and T cells that trigger ME/CFS.

Other Triggering Factors

Researchers don’t yet know the exact role most risk factors play in ME/CFS, but their importance appears to be growing.

Besides infections, factors believed to contribute to the development of ME/CFS in genetically predisposed people include:

  • Immune system abnormalities
  • Stressful conditions
  • Central nervous system abnormalities
  • Hormonal imbalance
  • Exposure to toxins

Women are diagnosed with ME/CFS between two and four times more often than men. This could be due in part to hormonal differences and events such as childbirth, menstruation, and menopause.

Recap

Infectious triggers may lead to immune-system changes in genetically susceptible people. Stress, hormones, and toxins may play a role as well.

Goals of Genetic Research

Genetic research is helping the medical community understand ME/CFS. Genetic research may lead to:

  • Genetic testing for ME/CFS risk
  • Objective diagnostic markers for identifying this hard-to-diagnose condition
  • Treatments aimed at the disease process instead of symptoms
  • Doctors being able to determine what treatments are most likely to work for you
  • Proper identification of ME/CFS subtypes, which many experts say is critical to understanding how to best manage a case

If these become a reality, it would drastically change the diagnosis and treatment of ME/CFS.

Currently, ME/CFS is a diagnosis of exclusion. That means doctors can only diagnose it by ruling out other possible causes of your symptoms.

Additionally, the U.S. Food and Drug Administration (FDA) has not approved any treatments for ME/CFS. Several drugs approved for other conditions are used for this condition (off-label), but many people don’t get adequate relief from them.

If Someone in Your Family Has ME/CFS

If you believe you're genetically predisposed to ME/CFS, you may be able to lower your risk of getting it by:

  • Avoiding infectious illnesses (e.g., get vaccinated, avoid sick people, wear a mask, wash your hands)
  • Getting prompt treatment for infectious illnesses
  • Living a generally healthy lifestyle (healthy diet, exercise, not smoking)

ME/CFS involves dozens of possible symptoms, including:

If you think that you might have chronic fatigue syndrome, see your doctor for an evaluation. Be sure to not only provide detailed information about your symptoms, but details on who in the family has ME/CFS and when they were diagnosed.

Chronic Fatigue Syndrome Doctor Discussion Guide

Get our printable guide for your next doctor's appointment to help you ask the right questions.

Doctor Discussion Guide Man

Summary

ME/CFS is not directly inherited, and its appearance in families isn't predictable. Rather, it involves a genetic predisposition, meaning your genetics set you up for a greater possibility of ME/CFS in the presence of other factors.

Infections are a significant one. Other possible triggers include stress, hormonal events, and exposure to toxic chemicals.

Genes involved deal with the immune system, metabolic function, hormones, your ability to learn, and more. Genetic research may lead to multiple improvements in how ME/CFS is dealt with.

A Word From Verywell

ME/CFS is hard to diagnose and treat. Doctors can't predict who will or won’t develop it, and they don’t know how to prevent it. Moreover, some doctors have little experience with it or may even question it being an actual diagnosis.

Remember that having ME/CFS symptoms and a family member with the condition doesn't mean you have it too. Symptoms overlap with a host of other conditions, and the condition is not inherited.

However, if your doctor seems to be dismissing the prospect of ME/CFS or you're not satisfied with the extent to which other diagnoses are being considered and ruled out, seek a second opinion.

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