CFS & Fibromyalgia Causes & Risk Factors Chronic Fatigue Syndrome Genetics Genetic Predisposition and Abnormalities of ME/CFS By Adrienne Dellwo linkedin Adrienne Dellwo is an experienced journalist who was diagnosed with fibromyalgia and has written extensively on the topic. Learn about our editorial process Adrienne Dellwo Medically reviewed by Medically reviewed by Grant Hughes, MD on February 20, 2021 linkedin Grant Hughes, MD, is board-certified in rheumatology and is the head of rheumatology at Seattle's Harborview Medical Center. Learn about our Medical Review Board Grant Hughes, MD Updated on March 18, 2021 Print Table of Contents View All Table of Contents Genetic Research Familial Patterns Genetic Predisposition Associated Genes Triggering Factors Chronic fatigue syndrome can run in families, which has led researchers to ask, “Is chronic fatigue syndrome genetic?” A lot of people with this disease also ask that question, wondering whether they’ll pass it on to a child or whether they have it because one of their parents did. Chronic fatigue syndrome, more recently named myalgic encephalomyelitis or ME/CFS, involves dozens of possible symptoms, including constant debilitating fatigue, disturbed sleep, cognitive dysfunction (“brain fog”), and—its hallmark symptom—an extreme reaction to exertion called post-exertional malaise. Researchers have much to still learn about ME/CFS, as it’s a complex disease involving multiple systems in the body. However, one thing many of them agree on is that ME/CFS isn’t an inherited condition, but it does involve a genetic predisposition and abnormalities in certain genes. MoMo Productions / Getty Images Why Genetic Research Matters The causes of ME/CFS remain unknown, but abnormalities in the immune, neurological, and endocrine systems have been described, which reflects the condition’s multi-system complexity. Given that, some people with this disease wonder why researchers “waste time” looking at genetics. While ME/CFS isn’t a genetic disorder, genetics has much to teach us about it. Through genetic research, we may gain: Objective diagnostic markers, which would help doctors identify this hard-to-diagnose condition Treatments aimed at addressing underlying causes of ME/CFS, which means they’re targeting the disease process and not just alleviating symptoms Genetic testing that may reveal who’s likely to develop ME/CFS and what treatments are most likely to work ME/CFS prevention based on genetic testing Proper identification of subtypes, which most experts believe is critical to understanding and treating the disease Currently, ME/CFS is a diagnosis of exclusion, meaning doctors diagnose it by ruling out other possible causes of your symptoms. Treatment Shortcomings Despite decades of research, people with ME/CFS still have no treatments approved by the U.S. Food and Drug Administration. While several off-label treatment options are available, many people don’t get adequate relief from them. Treating ME/CFS Chronic Fatigue Syndrome Doctor Discussion Guide Get our printable guide for your next doctor's appointment to help you ask the right questions. Download PDF Email the Guide Send to yourself or a loved one. Sign Up This Doctor Discussion Guide has been sent to {{form.email}}. There was an error. Please try again. Familial Patterns Research suggests the inherited portion of ME/CFS is only about 10% of the overall cause. This suggests that genetic factors combine with environmental factors to trigger the disease. In a study looking at first, second, and third-degree relatives of someone with ME/CFS, data suggest that the risk is greater even for more distant relatives. It’s unlikely that there’s one “ME/CFS gene,” though. Studies show that the pattern of cases within families doesn’t follow a predictable pattern like some diseases do. This leads experts to believe it’s more likely that many genetic variables are involved. Type of Relative Who That Is Increase in Risk 1st degree Parent, sibling, child 2.7 times 2nd degree Grandparent/child, aunt/uncle, niece/nephew, half-sibling 2.34 times 3rd degree First cousin, great-grandparent/child 1.93 times Source: Albright, et al. Genetic Predisposition While you may have inherited a genetic predisposition, or susceptibility, to ME/CFS, that doesn’t mean you’ll someday develop it. A genetic susceptibility is different from a hereditary disease: In a true genetic disease: If you inherit the gene, you either have or will eventually have the disease. With a 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 ME/CFS. Research suggests the inherited portion of ME/CFS is only about 10% of the overall cause. This means that it takes a genetic predisposition combined with other factors to trigger the disease. Examples An example of something that may combine with genetic predisposition to trigger ME/CFS, according to 2018 research, is numerous infections of the digestive tract or airways. In response to the infections, genetically susceptible may develop what are called “autoreactive B cells.” B cells are a part of the immune system that creates antibodies (proteins that are supposed to fight off infection). When B cells are autoreactive, it means they produce autoantibodies, antibodies that attack healthy tissues as though they were a dangerous invader, like a virus. In ME/CFS, these autoantibodies may target key enzymes that deal with energy metabolism, which researchers believe may lead to the hallmark symptom of ME/CFS: post-exertional malaise. Infection with the Epstein-Barr virus (EBV, which causes mononucleosis) is also believed to start a reaction in susceptible people that leads to abnormal activity from B cells and T cells (another type of immune cell) and triggers ME/CFS. What It Means to Have a Genetic Predisposition Associated Genes Researchers have identified a number of genes that may be involved in ME/CFS. One study found activity changes in nearly 1,200 sites that correspond to more than 800 genes. Various studies have found changes in genes that deal with: Integrity of the blood-brain barrier Neuroplasticity (ability of the brain to make new connections in response to learning) Immune-system activation not related to infection Regulation of the immune system Metabolic function, including the processing of sugars and fats Activity of hormones (naturally produced glucocorticoids, estrogen, androgens) Receptors of the neurotransmitter glutamate Sensitivity to glucocorticoids Stress-response system regulation Enzymes that affect DNA expression T cell function One study found more than 100 changes to genes associated with T-cells alone. Some immune-system changes may even be an underlying mechanism of ME/CFS. Other Triggering Factors So far, researchers don’t know the exact role of most causal and risk factors in ME/CFS, although, as demonstrated by the research cited above, they appear to be gaining important ground. Factors beyond genetics that are believed to contribute to the development of the disease include: Infection, especially viral, such as with EBV Flu-like illness 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 than men. This could be accounted for, at least in part, by hormonal differences and reproductive events such as childbirth, menstruation, and menopause. Preventing ME/CFS If you believe you or someone close to you is genetically predisposed to ME/CFS, you may be able to take some steps to make the disease’s onset less likely: Avoid infectious illnesses (e.g., get vaccinated, avoid sick people, wear a mask, wash hands) Get prompt treatment for infectious illnesses Live a generally healthy lifestyle (healthy diet, exercise, not smoking) A Word From Verywell ME/CFS is difficult to diagnose and treat. Right now, doctors don’t know enough about ME/CFS to predict who will or won’t develop the disease. They also don’t know how to prevent it. Genetic research could one day give them objective biomarkers for diagnosis, targeted treatments, genetic testing to see who’s susceptible, and the necessary tools to delay or prevent its onset. Causes and Risk Factors for ME/CFS Was this page helpful? Thanks for your feedback! Learn about treatment and lifestyle changes to cope with fibromyalgia and chronic fatigue syndrome. Sign Up You're in! Thank you, {{form.email}}, for signing up. There was an error. Please try again. What are your concerns? Other Inaccurate Hard to Understand Submit Article Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Herrera S, de Vega WC, Ashbrook D, Vernon SD, McGowan PO. Genome-epigenome interactions associated with myalgic encephalomyelitis/chronic fatigue syndrome. Epigenetics. 2018;13(12):1174-1190. doi:10.1080/15592294.2018.1549769 Albright F, Light K, Light A, Bateman L, Cannon-Albright LA. Evidence for a heritable predisposition to chronic fatigue syndrome. BMC Neurol. 2011;11:62. doi:10.1186/1471-2377-11-62 de Vega WC, McGowan PO. The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome: deciphering complex phenotypes. 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Published 2018 Jul 23. doi:10.1371/journal.pone.0201066 U.S. Department of Health & Human Services, Office on Women’s Health. Chronic fatigue syndrome. Updated April 26, 2019.