More than three decades after myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), gained recognition as a medical condition, new research from the University of East Anglia points to genetic factors underlying chronic fatigue symptoms shared across several diseases. The study, published recently in the Journal of Translational Medicine, identifies epigenetic changes—modifications that affect gene expression without altering DNA sequence—that may contribute to the exhaustion and cognitive difficulties common to ME/CFS, long Covid, multiple sclerosis (MS), rheumatoid arthritis, and post-traumatic stress disorder (PTSD).

The research team analyzed the genetic profiles of patients with these five illnesses, uncovering a common “switch” that appears to disrupt energy production in cells, potentially explaining the pervasive fatigue experienced by approximately 5.7 million people in the United Kingdom affected by these conditions. Lead researcher Professor Dmitry Pshezhetskiy underscored that these epigenetic changes also influence metabolism, immune response, and stress regulation, signaling a physiological basis for symptoms often dismissed as psychosomatic.

“This discovery offers objective, blood-based biological evidence of disease,” Pshezhetskiy said, noting that patients with these disorders report strikingly similar symptoms, including overwhelming fatigue, brain fog, difficulty concentrating, and sleep disturbances. The findings may open the door to developing a unified treatment approach targeting the underlying epigenetic mechanisms.

This study adds to a growing body of work supporting physical causes of ME/CFS and related syndromes. Previous research, including a 2023 Australian study published in Cell, found concurrent disruptions in energy generation and immune regulation in ME/CFS patients. Other investigations have indicated that immune system hyperactivity might trigger chronic fatigue by eliciting flu-like symptoms even in the absence of infection.

For patients such as Emma Slack, diagnosed with ME/CFS in 2017 after years of misdiagnoses and skepticism, the discovery of a genetic component represents a significant step toward validating their experience. Slack, from Newcastle, first developed symptoms in 2008 following a suspected viral infection. Despite a history of high physical activity, she has since endured persistent fatigue, cognitive impairment, and sleep problems, often exacerbated by exertion. Her diagnosis came after years during which her symptoms were attributed to anxiety and dismissed by some medical professionals. Slack highlighted the ongoing challenges faced by many in obtaining appropriate recognition and care for the condition, citing personal difficulties during pregnancy and breastfeeding when symptoms intensified.

Professor Pshezhetskiy hopes the identification of epigenetic markers will lead to a blood test for faster diagnosis and the development of targeted epigenetic therapies to restore normal cellular function. “This would help prevent patients from enduring prolonged periods of misdiagnosis and dismissal,” he said.

However, some experts urge caution regarding the new findings. Dr. Charles Shepherd, medical adviser to the ME Association, described the conclusions as still preliminary, emphasizing the need for further research to understand how to effectively repair immune dysfunction and impaired energy production. “Until we have a clearer grasp of the mechanisms, treatments will primarily address symptoms,” he said, while acknowledging the importance of growing recognition of chronic fatigue syndromes.

Similarly, Professor Carmine Pariante of King’s College London noted that the study does not introduce novel mechanisms but welcomed its role in reinforcing existing knowledge and supporting patients living with these often debilitating conditions.