By Dr. Jen Welter, PT, DPT, Fellow of Pain Sciences
Thrive Whole Person Health, LLC

Science not Stigma

For too long, people with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) have experienced dismissal, misunderstanding, or outright disbelief from both medical systems and society. Recent progress, however, offers long‑awaited validation.  The groundbreaking work of the DecodeME study from the University of Edinburgh has identified genetic signals associated with ME/CFS. These findings do more than push science forward—they affirm the biological reality of the illness, refute old myths, and point toward new directions for treatment.

What is the DecodeME Study?

The DecodeME project is a genome‑wide association study (GWAS) designed to identify genetic risk factors for ME/CFS. Its first analysis compared DNA from 15,579 people diagnosed with ME/CFS vs. 259,909 control individuals without it, all of European ancestry, to control for confounding due to population genetics.

What Did They Find?

• Eight genetic loci (regions) across the genome where people with ME/CFS are more likely to carry certain genetic variants.
• Immune system & nervous system involvement: Many of these loci are in or near genes that play roles in infection detection/response, immune regulation, neurodevelopment, or nervous system signaling. One locus is also previously linked to multi‑site chronic pain.
• No overlap with genes for depression or anxiety among those eight signals. This helps clarify that these genetic markers are not merely reflections of mental health disorders, but are distinct – though co‑morbid mental health issues may still arise.
• These variants explain only part of the genetic contribution to ME/CFS risk.  The common variants found account for only a portion of the total risk. That means many other factors—other genetic variants, environmental insults, epigenetics, neuroimmune interactions—are likely critical.
• No identified genetic basis yet for why ME/CFS is more common in women. The study did not find signals explaining the sex skew. Also, X and Y chromosomes were not assessed in this initial work.

Why This Matters

Validation!   It’s NOT all in your head!

These findings confirm that there are measurable, inherited biological differences in many people with ME/CFS—not just after the illness starts but predispositions that exist before. This helps counteract stigma and the suggestion that “it’s all in your head.”

Targets for research and treatment. Knowing where in genome/biology these signals lie gives scientists credible leads: immune dysregulation, nervous system function, infection response. These are likely pathways to develop diagnostics, treatments, maybe even preventative strategies.

But to be clear, this is not a diagnostic test (yet). The signals are probabilistic, not deterministic. What does that mean?  Many people without ME/CFS carry these variants; many with ME/CFS will have combinations of risks that cannot be easily distilled into a simple genetic risk profile at present.

The Key – Tapping into Neuroplasticity & Epigenetic Modulation

Given that genetics set the stage but do not write the full script, treatments and care approaches that can influence gene expression (epigenetics) and the brain’s ability to change and adapt (neuroplasticity) are especially relevant.

Epigenetic modulation refers to interventions that alter how genes are expressed without changing the underlying DNA. These include lifestyle factors (nutrition, sleep, stress management), pharmacologic agents, possibly even environmental exposures.

Neuroplasticity includes therapies that engage the brain and nervous system: cognitive rehabilitation, graded movement, neuromodulation techniques (e.g. non‑invasive brain stimulation, mindfulness, biofeedback, vagal nerve stimulation), helping rewire or retrain neural circuits that may be dysregulated in ME/CFS.

These approaches do not ignore the genetic underpinnings, but rather work with them—leveraging the fact that genes may predispose, but environment and treatment can moderate outcomes.

A Turning Point

The DecodeME findings are a turning point. For patients, they bring long overdue validation.  This is not a disease of weak will, psychogenic misinterpretation, or character flaw. The biology is real, measurable, and now scientifically traced back in part even to inherited risk factors. But biology is complex, and genes are only one part of the picture.

To alter the trajectory of illness, we need treatment strategies that do more than mask symptoms: those that engage the brain, the immune system, and the epigenome—to harness plasticity and resilience. As a clinician and someone who cares deeply about people with ME/CFS, I believe the way forward must integrate biomedical research with a whole-person approach. This study opens the door. Now we must walk through it.

Learn more about the whole person approach to health at www.ThriveWholePersonHealth.com

References & Further Reading

• DecodeME “Initial DNA Results” summary. https://institute-genetics-cancer.ed.ac.uk/decodeme-the-worlds-largest-mecfs-study/initial-decodeme-dna-results
• Preprint: Initial findings from the DECODEME genome‑wide association study of myalgic encephalomyelitis/chronic fatigue syndrome. https://www.medrxiv.org/content/10.1101/2025.08.06.25333109v1.full-text