Scientists have found the first robust evidence that people’s genes affect their chances of developing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), a mysterious and debilitating illness that has been neglected and dismissed for decades by many in the medical community.
Early findings from the world’s largest study into the genetics of the condition pinpointed eight regions of the human genome that were substantially different in people with an ME/CFS diagnosis compared to those without the illness.
The discovery suggests that several variants of genes commonly found in the population raise the risk of developing the illness, though many people will carry the variants and never acquire it.
Prof Chris Ponting, an investigator on the DecodeME study at the University of Edinburgh, called the results “a wake-up call” that showed a person’s genetics could “tip the balance” on whether they would develop ME/CFS.
“These provide the first robust evidence for genetic contributions to ME,” Ponting said. “There are many genetic variants that apply across the genome that predispose people to be diagnosed with ME.”
More research is needed to develop diagnostic tests or screenings to identify people at high risk of ME/CFS. But scientists called the work a milestone that put the illness on an equal footing with other debilitating diseases and opened potential avenues for treatments.
“This really adds validity and credibility for people with ME,” said Sonya Chowdhury, chief executive of Action for ME and a DecodeME co-investigator. “We know that many people have experienced comments like ‘ME is not real’. They’ve been to doctors and they’ve been disbelieved or told that it’s not a real illness.”
Despite its long history, scientists understand very little about the causes of ME/CFS, though most patients report an infection before symptoms first appear. Typical symptoms include extreme tiredness, sleep problems, brain fog and a worsening of symptoms after physical or mental activities, known as post-exertional malaise, which can take weeks to recover from.
It is estimated that 67 million people are affected by ME/CFS at an annual cost to the global economy of tens of billions of pounds. In the UK, the annual economic toll is calculated at more than £3bn. There is no test or cure for the illness.
The DecodeME study, a collaboration between Edinburgh University, ME charities and patients, was launched in 2022 to explore whether genes play a role in who develops ME/CFS. For the latest work, researchers analysed 15,579 DNA samples from 27,000 people with ME/CFS and more than 250,000 people without the illness.
The eight genetic regions that stood out in people with ME/CFS contain genes involved in immune defences and the nervous system. It will take more work to unpick the biology, but some gene variants may make people more vulnerable to ME/CFS by compromising their ability to fight bacterial and viral infections. Another genetic difference seen in ME/CFS is known from people with chronic pain, a symptom that many with ME/CFS also experience. “Overall, what is happening here is the genetics align with how people with ME have described their illness,” Ponting said.
Andy Devereux-Cooke, a DecodeMe co-investigator, said the findings would be huge for patients. “The vast majority of the patient population essentially has been abandoned in one way or another, by families, the government, the medical system,” he said. “This will be huge for the patient population. Even though it does not provide all the answers [and] it does not provide practical assistance, it is a welcome drop in the ocean towards turning the tide.”
Among the many questions that remain is why ME/CFS affects far more women than men. Diagnoses are four times more common in women, but the study found no genetic explanation. Another question is whether long Covid overlaps with ME/CFS. While many symptoms are similar, the researchers found no genetic link between the two. “One of the key things we’re doing is enabling others to use their different approaches to ask and answer the same question,” said Ponting.
Prof Anne McArdle, who studies ME/CFS at the University of Liverpool, said the results, which have not yet been published in a peer-reviewed journal, provided “a solid basis” for future work that would hopefully help accelerate the development of a treatment for the devastating illness.
Dr Beata Godlewska, who studies ME/CFS at the University of Oxford, recently used magnetic resonance spectroscopy to scan the brains of people with ME/CFS and long Covid. Those with ME/CFS but not long Covid had high levels of lactate in the anterior cingulate cortex, a brain region that integrates information about effort and emotion. This points to disrupted energy metabolism in the brain, and impaired mitochondria, the battery-like structures that provide energy inside cells.
Godlewska said “It’s a very sad fact that people with ME/CFS are still disbelieved and the disease has been so neglected, especially when it comes to research funding. Hopefully this study will come with a benefit of both fighting the stigma, and convincing research funders that this is a truly biological condition.”
