A recent genome study has identified common biological mechanisms underlying fatigue across several distinct medical conditions, potentially transforming the understanding and diagnosis of these often misunderstood disorders. The research, led by Professor Dmitry Pshezhetskiy at the University of East Anglia, examined epigenetic changes in patients with long Covid, post-traumatic stress disorder (PTSD), rheumatoid arthritis, multiple sclerosis, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Each of these conditions affects millions in the United Kingdom and is characterized by severe, long-lasting fatigue accompanied by symptoms such as brain fog and difficulties with sleep or concentration. Despite this shared symptomatology, the diseases have traditionally been viewed as unrelated, with complex and often slow diagnostic processes, partly because no single reliable blood test exists for any of them.

Pshezhetskiy, a clinician and epigenetics researcher, highlighted the challenges faced by patients, particularly those with ME/CFS. “Many of them are very young. They feel horrendous, they’re exhausted and have multiple other symptoms. They wait five or six years for a diagnosis,” he said. Epigenetics focuses on how environmental factors and experiences such as stress, illness, pollution, exercise, and nutrition influence gene expression without altering the underlying DNA sequence.

The study involved analyzing a large digital database of genomes from individuals diagnosed with one of the five conditions. Rather than finding common genetic mutations across patients with the same illness, the team discovered shared epigenetic modifications—referred to as “flipped switches”—affecting different genes across the disorders. These modifications disrupt biological systems governing energy production, metabolic regulation, and stress response.

This convergence at the level of biological system dysregulation provides a mechanistic explanation for chronic fatigue across ostensibly disparate diseases. According to Pshezhetskiy, this finding brings scientists closer to developing objective diagnostic tools, such as blood tests, to detect fatigue based on its epigenetic markers rather than relying solely on subjective questionnaires or physical capacity evaluations.

The implications of this study may be significant for future treatment approaches. While clinical trials for new diagnostics or therapies are still forthcoming, the research challenges long-held skepticism about the existence and severity of fatigue-related illnesses and underscores their biological basis.

Pshezhetskiy described the work as approaching “a biological unifying theory of fatigue,” emphasizing its potential to illuminate the mechanisms behind fatigue symptoms that have remained unexplained. He is currently planning a larger trial to further explore epigenetic patterns across additional conditions associated with fatigue, suggesting that the approach might be broadly applicable beyond the initial five disorders studied.