Study Links Five Illnesses Through Shared Fatigue Biology

Key Developments:

• Five illnesses show common biological patterns
• Researchers identify links in immune pathways
• Study may aid future diagnostic research

(Medical Xpress) — September 03, 2026: Scientists studying chronic fatigue have found biological links between five different illnesses, raising the possibility that some of the conditions may involve related processes inside the body.

The research examined myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), long COVID, post-traumatic stress disorder (PTSD), rheumatoid arthritis and multiple sclerosis (MS). Although the diseases have different origins, researchers found that genetic changes associated with them can converge within wider biological networks.

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The study was led by the University of East Anglia (UEA) with Oxford BioDynamics and collaborators from the London School of Hygiene and Tropical Medicine and Cornwall Partnership NHS Foundation Trust. It was published in the Journal of Translational Medicine.

Instead of comparing DNA only as a sequence of individual genes, the researchers examined how genetic material is arranged and interacts in three dimensions. They used the EpiSwitch Orion platform to analyse previously available genomic information from the five conditions.

This approach produced a different picture from a conventional gene-by-gene comparison. Researchers found limited direct genetic overlap between the diseases, but identified connections when the genes were considered as part of larger regulatory systems.

Image courtesy of Vitaly Gariev.

Professor Dmitry Pshezhetskiy, the study’s lead researcher, said the conditions had traditionally been treated as separate disorders because their triggers vary considerably.

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“Until now, illnesses including long COVID, PTSD, ME/CFS, multiple sclerosis and rheumatoid arthritis were viewed as seemingly unrelated,” Pshezhetskiy said.

The team found that several biological processes appeared repeatedly across the conditions. These included immune signalling, inflammatory responses, energy production within cells, metabolism and mechanisms involved in the body’s response to stress.

The researchers believe these connections could offer one explanation for why patients with otherwise different illnesses can report comparable problems, including severe tiredness, cognitive difficulties, disrupted sleep and reduced daily functioning.

Pshezhetskiy said the findings point towards “a biological unifying theory of fatigue”, although the study does not establish that the five illnesses have a single cause.

The research also identified highly connected genes that could warrant further investigation. One of these, LAG3, was highlighted in the ME/CFS analysis because of its relationship with regulation of immune cells and T-cell exhaustion. The researchers stressed that identifying such a gene does not prove that it causes the disease.

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The researchers say the work could eventually have implications for diagnosis. ME/CFS and long COVID currently lack a universally accepted laboratory test, meaning diagnosis generally relies heavily on clinical assessment and reported symptoms.

“We hope our work could pave the way for objective blood tests capable of identifying underlying biological signatures,” Pshezhetskiy said.

However, such tests are not yet available as a result of this study. The findings need to be reproduced and validated through additional research before any potential biomarker could be considered for routine clinical use.

Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Schematics of the datasets collected from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients and healthy controls. CREDIT: nature.com.

The study also builds on earlier work involving 3D genomic analysis. Research reported in 2025 described an EpiSwitch-based blood test for ME/CFS with promising results, but further validation was still required before clinical application.

The researchers’ latest analysis therefore represents a potential direction for future investigation rather than a new treatment or diagnostic method.

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The findings are also consistent with wider research suggesting that different chronic illnesses can share biological features. A separate ME Research UK-supported study comparing fatigue across several chronic disease groups found similarities in the nature of fatigue, while also reporting that people with ME/CFS experienced particularly high overall fatigue levels.

Researchers say further studies will be needed to determine whether the biological connections identified in the latest work can be confirmed in patient populations and whether they can ultimately contribute to improved diagnosis or treatment.

For now, the study offers a possible explanation for an important medical puzzle: why illnesses with very different triggers can sometimes produce similar patterns of prolonged exhaustion and other disabling symptoms.

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