Why we should celebrate the findings of the DecodeME genetic study

A landmark genetic study brings new hope for the ME/CFS community. The groundbreaking DecodeME project, the largest of its kind in the world, has successfully identified the first robust genetic links to myalgic encephalomyelitis, providing long-awaited scientific validation that this devastating illness is rooted in biology.

Key discoveries made by the study shine a light on the specific immune and neurological mechanisms which underpin this condition. This research offers clear directions for future research in ME/CFS. More importantly, it paves the way to identifying proper diagnosic tools and effective treatments, and a deeper understanding for millions around the world.

Here we describe the key findings from the DecodeME genetic study and  why these findings are so important.

What was the goal of the study?

For decades, the biological causes of ME/CFS have been poorly understood, leading to a lack of effective treatments. People with ME/CFS have frequently not been understood or believed by healthcare professionals. The DecodeME genetic study was set up to change this;  its primary goal was to identify common genetic variations that influence the risk of developing ME/CFS, which would point researchers toward the underlying biological mechanisms of the disease.

How was the DecodeME genetic study undertaken?

The study was co-produced with people who have ME/CFS, ensuring the research was shaped by the community's priorities and experiences.

• Participants: the team recruited a huge number of people -  21,620 people in the UK with a professional diagnosis of ME/CFS who also reported the hallmark symptom, post-exertional malaise (PEM) were included in the study

  
  

• Method: researchers performed a Genome-Wide Association Study (GWAS), which compares the DNA of people with a condition to the DNA of healthy controls. They analysed the genetics of 15,579 participants with European ancestry against 259,909 controls from the UK Biobank

  
  

• Rigour: the study used strict diagnostic criteria and state-of-the-art genetic analysis techniques to ensure robust results.

Key Findings

1. First robust genetic links to ME/CFS

The DecodeME genetic study discovered eight distinct regions of the genome significantly associated with ME/CFS. This is the first robust genetic evidence for the disease, proving that a predisposition to ME/CFS is, in part, genetic and biological.

2. Pointing to biological mechanisms

The genetic regions (loci) contain genes that point to two primary biological systems being involved:

• Immunological dysfunction: several genes are involved in the body's response to infection:

  • RABGAP1L is involved in expelling bacteria and limiting viral replication.

  • BTN2A2 and TRIM38 help regulate immune cell responses to infection and prevent excessive inflammation

  • OLFM4 dampens inflammatory and antibacterial responses

    
    

• Neurological Dysfunction: one gene is strongly linked to pain and brain function:

  • CA10 is involved in regulating communication between brain cells (neurons). The study found this specific genetic signal is shared with multisite chronic pain, providing a biological explanation for why over 86% of participants experience pain.

3. No genetic overlap with depression or anxiety

A crucial finding of the Decode genetic study was that none of the eight genetic signals identified were shared with depression or anxiety. This provides strong genetic evidence that ME/CFS is a distinct physical disease, not a psychological condition, directly countering a long-standing and damaging misconceptions.

4. Infection as a trigger

The genetic association near the OLFM4 gene was significantly stronger in people whose illness was triggered by an infection (which was ~63% of participants). This suggests that these genetic differences may affect how people respond to infections, potentially increasing the risk of developing ME/CFS afterwards.

5. The sex-bias mystery remains

While ME/CFS affects far more women than men (~85% of participants were female), the DecodeME genetic study found no evidence that the discovered genetic risk variants are stronger in women. The reason for the female bias is therefore not explained by these common genetic variants and must lie in other factors, such as hormones, environmental exposures, or biological differences.

6. No single gene is the cause

ME/CFS is not caused by a single gene. The findings confirm it is a complex disease where many genetic variations, each with a small effect, combine with environmental triggers (like infection) to influence risk.

Implications of the DecodeME genetic study

1. Validation and legitimacy: This research provides the strongest evidence yet that ME/CFS is a real, biological disease with a genetic basis. It offers tangible proof to counter the historical stigma and disbelief faced by patients from society, and sometimes even from healthcare professionals.

   
   

2. A path to better treatment and diagnosis: By identifying specific genes and biological pathways involved, the study provides clear new targets for drug development. In the future, this could lead to effective treatments that modulate the immune system or target neurological pain pathways. It also opens the door to eventually understanding sub-types of ME/CFS, which could lead to more personalised treatment approaches

   
   

3. A foundation for future research: DecodeME genetic study creates a powerful resource for the scientific community. The genetic data is being made available to qualified researchers worldwide to accelerate progress. Furthermore, thousands of participants consented to be re-contacted, creating a ready-made group for future clinical trials.

   
   

4. Distinction from mental health conditions: The clear genetic separation from depression and anxiety should help to re-frame the narrative around ME/CFS, guiding research funding and medical training toward its true biological nature.

Conclusion

The DecodeME genetic study is a transformative moment for ME/CFS research. It successfully moves the conversation from suspicion and neglect to one focused on specific biological mechanisms involving immunity and neurology. While it does not provide an immediate cure, it provides a crucial foundational map that will guide scientists toward better diagnostics, treatments, and ultimately, a deeper understanding of this devastating disease. It validates the lived experiences of patients and offers real hope for the future.

Webinar by the research team recorded on 14^th August 2025

You can watch the webinar which describe the Initial DNA results and in which researchers Sonya Chowdhury, Chris Ponting and Andy Devereux-Cooke describe these results, what they mean for people with ME/CFS, what happens next and a Q& A session. Here is the link

Reference

Decode ME collaboration (2025). Initial findings from the Decode ME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome. Preprint. University of Edinburgh. https://www.research.ed.ac.uk/en/publications/initial-findings-from-the-decodeme-genome-wide-association-study-