Key genetic differences found in people with ME/CFS

Scientists have discovered that people diagnosed with ME/CFS have significant differences in their DNA, offering the first robust evidence that genes contribute to a person’s chance of developing the disease.

Older woman pictured from behind, sat on a bed looking out of a window

Initial findings have uncovered eight areas of genetic code in people with ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) that are markedly different to the DNA of people without the condition. 

Results from the landmark DecodeME study, the largest of its kind in the world, provide a major step forward in understanding the biological roots of ME/CFS and suggest that both the immune system and nervous system are involved in its development, experts say.

The findings – first reported in a pre-print publication, or unpublished study – represent a milestone in ME/CFS research and can now help guide the search for effective treatments, placing this long-neglected disease on equal terms with other debilitating conditions, researchers say.  

Debilitating illness

ME/CFS’ key feature, known as Post-Exertional Malaise (PEM), is a disproportionate worsening of symptoms following even minor physical or mental activity. Other symptoms include pain, brain fog and extreme energy limitations that do not improve with rest. 

Very little has been known about the causes of ME/CFS and there is currently no diagnostic test or cure. It is believed to affect around 67 million people worldwide. 

Genetic discovery

For the new study researchers analysed 15,579 DNA samples from the 27,000 people with ME/CFS participating in DecodeME – the world's largest data set of people with the disease.

They found eight regions of DNA where genetic differences were significantly more common in people with ME/CFS than in the general population.

These differences – also known as genetic signals – involve genes linked to the immune and nervous systems.

Biological insight

At least two of the genetic signals relate to how the body responds to infection, which aligns with longstanding patient reports that the onset of symptoms often followed an infectious illness. 

Another has previously been identified in those experiencing chronic pain, a symptom commonly described by those living with ME/CFS.

As a person’s DNA does not change over time, experts say the genetic signals identified would not have developed because of ME/CFS and are therefore likely to reflect the causes of the disease.

Populations used in this initial study were limited to those from European ancestries. DecodeME research studying DNA data from all ancestries is ongoing.

Global call

Researchers say the findings are not yet ready to inform treatment or diagnosis but offer vital clues to the disease’s origins and could guide future drug development.

The DecodeME team is now calling on researchers from around the world to access its rich dataset and help drive forward targeted studies into ME/CFS, particularly those linked to the eight newly identified genetic signals.

This is a wakeup call. These extraordinary DNA results speak the language of ME/CFS, often recounting people’s ME/CFS  symptoms. DecodeME’s eight genetic signals reveal much about why infection triggers ME/CFS, and why pain is a common symptom. ME/CFS is a serious illness and we now know that someone’s genetics can tip the balance on whether they are diagnosed with it.

DecodeME has revealed genetic results, which should prove game changing in the ME/CFS research field, and that also align with decades of patients reporting on their experiences. These results will not mean that a test or cure will be developed straight away, but they will lead to a greater understanding of ME/CFS. DecodeME also shows the incredible level of support that the ME/CFS patient community can give to research that involves them on a deep and meaningful level. Without the community, we could not have achieved all that we have.

These results are ground-breaking. With DecodeME, we have gone from knowing next to nothing about the causes of ME/CFS, to giving researchers clear targets. This brings ME/CFS in line with other long-term diseases which have genetic components. We are shining a laser light on eight precise areas of DNA, so that highly focused research can now be carried out. We hope this attracts researchers, drug developers, and proportionate funding to ME/CFS – and speeds up the discovery of treatments.

Collaborative study

DecodeME was launched in 2022 to explore whether genes play a role in who develops ME/CFS.

As well as genetic analysis, the study includes questionnaire data, helping researchers better understand the lived experiences of those with the disease.

The study has previously reported that women with ME/CFS have more symptoms and co-occurring conditions than men. 

DecodeME is a collaboration between the University of Edinburgh, the charity Action for ME, the Forward ME alliance of charities, and people with ME/CFS. It is funded by the Medical Research Council and National Institute for Health and Care Research.

Related links

Read the full pre-print paper here

DecodeME

MRC Human Genetics Unit

Action for ME

Forward ME

Image credit: Westend61 via Getty Images

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2025
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