For millions of people, fatigue is not a bad night's sleep. It is a heaviness that does not lift with rest, a mental fog that turns simple errands into an ordeal, and a symptom their doctor cannot easily explain.
Now a UK research team says the exhaustion in five very different diagnoses may spring from the same underlying biology.
The analysis, published in September 2026 in the Journal of Translational Medicine, was led by Professor Dmitry Pshezhetskiy at the University of East Anglia's Norwich Medical School with Oxford BioDynamics.
It looked across myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), long COVID, post-traumatic stress disorder (PTSD), rheumatoid arthritis and multiple sclerosis.
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Five conditions, five overlapping systems
At the level of single genes, the diseases barely resembled one another.
What the researchers describe is a convergence one level up, on shared regulatory networks that steer immune and inflammatory signaling, mitochondrial energy production, metabolic regulation, stress-response pathways and neuroendocrine signaling.
"Although these conditions are triggered by completely different events, they may ultimately disrupt the same fundamental biological systems and produce the similarly devastating exhaustion experienced by millions worldwide," Pshezhetskiy said, according to a summary reported by News-Medical.
He described the pattern as "something approaching a biological unifying theory of fatigue."
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How the team looked at DNA differently
Rather than reading DNA letter by letter, the group used a platform called EpiSwitch Orion to map the three-dimensional shape of the genome.
That matters because a chromosome is not a straight line inside a cell.
"DNA is folded in our cells, so regions far apart in the linear sequence can touch, and those contact points are where genes get controlled," said Dr. Ewan Hunter, chief data officer at Oxford BioDynamics.
The team combined published genome-wide association data for long COVID, PTSD, rheumatoid arthritis and multiple sclerosis with earlier 3D genomic data from ME/CFS patients.
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No new patients were sampled. One flagged hub gene, LAG3, is linked to T-cell exhaustion, a state in which immune cells become depleted after long stretches of activation.
Why it matters for treatment
If different diseases funnel into the same biological chokepoints, a drug that eases fatigue in one might, in principle, help in another.
That is a long way from a prescription pad, but it reframes fatigue as a target in its own right rather than a leftover symptom.
The National Institute of Mental Health puts the annual PTSD prevalence at about 3.6 percent of adults, which works out to millions more.
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What independent scientists caution
Not everyone is convinced the paper delivers on its bigger claim.
Professor Chris Ponting, chair of medical bioinformatics at the MRC Human Genetics Unit at the University of Edinburgh, said in comments collected by the Science Media Centre that the study's proprietary methods make its findings hard to check.
"Unfortunately, the 2026 study's claims are impossible to evaluate because the computational methods they used are proprietary," Ponting said.
Dr. Sjoerd Beentjes of the University of Edinburgh added that the "biological unifying theory of fatigue" language "seems an overstatement," while Professor Carmine Pariante of King's College London noted the analysis relied on already published datasets and did not identify novel mechanisms.
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For patients, the practical takeaway is narrower than the headline suggests.
Nothing about this analysis changes current diagnosis or treatment, and anyone experiencing persistent, unexplained fatigue should still talk to their doctor.
Oxford BioDynamics says a blood-based ME/CFS test built on the same EpiSwitch platform is now in validation.
This article is made and published by Ida-Marie Palm Varbæk, who may have used AI in the preparation.