Chronic fatigue syndrome or myalgic encephalomyelitis (ME/CFS) is a debilitating and long-neglected disease that experts typically dismissed as psychosomatic for decades.
To this day, some physicians still believe the illness is all in a patient’s head, but the largest genetic analysis of its kind suggests there are real biological origins.
A UK research project, called DecodeME, has investigated the genome-wide associations and uncovered eight possible signals associated with ME/CFS.
The preprint findings, which have not yet been published or peer-reviewed, suggest that an individual’s genes at least partly contribute to their chances of developing ME/CFS.
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One of the eight genetic variants “nicely overlays” a signal that was previously linked to chronic pain, a common symptom of ME/CFS explains the project leader of DecodeME, bioinformaticist Chris Ponting from the University of Edinburgh.
In addition, three of the eight signals are known to act as first responders to viral or bacterial infections. The findings could help explain why ME/CFS patients often report an infection before their first symptoms, and why numbers have surged since the pandemic.
“DecodeME’s results, grounded in the principles of statistical genetics, now place ME/CFS research on a firm biological foundation,” concludes the DecodeME team of more than 50 researchers. This “should help to reduce the stigma of the illness,” they add.
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Neuropsychiatrist Alan Carson from the University of Edinburgh, who was not involved in the study, says it is “by someway the largest study ever conducted on genetics of CFS/ME.”
DecodeME’s analysis brought together more than 16,000 patients, most of whom are female and of European descent. The criteria for diagnosis was stringent so that only the most clear-cut cases were included.
Patients must have had an official diagnosis of ME/CFS as well as a key symptom, called post-exertional malaise, which essentially translates to undue fatigue following exercise or other energy-consuming activities, including concentrating or socializing.
The findings revealed over a dozen genetic signals linked to ME/CFS, but only eight could be replicated in a second dataset, including more than 13,000 cases.
A third dataset of more than 14,000 cases failed to reproduce the results. This may have been due to differences in how ME/CFS was defined and diagnosed.
While these eight genome-wide associations are not exclusive to those with ME/CFS, the findings suggest that they are more likely to occur in those with the disease.
Many of the eight gene signals were expressed in brain tissue, including the ones associated with pain and the immune system.
“Drugs targeting these genes’ proteins might help protect against the consequences of microbial infection and therefore could reduce the risk of acquiring ME/CFS,” the authors suggest.
The signals are modest, and we don’t yet know what they mean. While there are limitations to the research, University of Hertfordshire geneticist Alena Pance, who was also not involved in the study, says the study is a “great advance towards understanding the illness better.”
But while Carson agrees the research is important, he sees a long road ahead. Carson points out that in disorders like depression, finding a few associated genes has not advanced our understanding of the disease or improved treatments just yet.
Still, important strides are being made with the help of patients. Ponting and his team argue that their recent findings help explain the heritable component of ME/CFS, improve the likelihood of finding effective drugs, and place the disease on more equal terms with other common genetic conditions.
“We’ve gone from knowing almost nothing about the causes of ME to having specific genetic information to delve much deeper into,” says study contributor Sonya Chowdhury, the CEO of UK health charity, Action for ME.
“For decades people with ME have asked to be heard, and now science is catching up.”
The research is available via preprint here.
