On the 14th of September, MedRXiv published a preprint paper entitled ‘Seven replicated genomic associations of myalgic encephalomyelitis/chronic fatigue syndrome: a biobank study' (Slaughter et al 2026). This is a genome wide association study involving 1268 people with ME/CFS and healthy controls who were obtained from the UK Biobank.
AI Summary (checked by MEA)
- Seven genetic associations were replicated across independent cohorts, identifying potential ME/CFS risk loci.
- Citrate lyase beta-like (CLYBL) showed particularly strong evidence for a potential biological link to ME/CFS.
- No significant gene–sex or gene–deprivation interactions survived multiple-testing correction.
- DecodeME did not replicate the four tested associations, suggesting effects may be smaller or cohort-specific.
- Conclusion: The findings provide promising genetic leads, however larger studies and further validation are needed before causal mechanisms can be established.
Lay Summary (as provided on PDF)
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common and disabling illness with a variety of symptoms. Additionally, little is known about the biological mechanisms that cause ME/CFS. The variety of symptoms and its unknown cause can make it difficult for healthcare professionals to diagnose people with ME/CFS reliably. This poses a significant challenge for ME/CFS research, as misdiagnoses may lead to errors in conclusions drawn from its study.
Previously, studies have attempted to find biological mechanisms for ME/CFS by comparing the DNA of people with ME/CFS with the DNA of people without ME/CFS. These studies have identified regions of DNA linked to the illness; however, none of these links have been found in other ME/CFS studies. In our work, we compare the DNA of people with ME/CFS to the DNA of people without ME/CFS, where ME/CFS status is supported by multiple lines of evidence to reduce the likelihood of
misdiagnoses in the participants selected for the study. We then use similar selection strategies, using multiple lines of evidence to repeat the study in independent groups of people.
By doing so, we found seven regions of DNA linked to ME/CFS status in more than one study. Some of these links are close to or located in regions of DNA called genes. Genes produce molecules known as proteins, which are responsible for many functions in the human body. It is not currently possible to determine exactly whether genes near disease linked regions of DNA cause disease, so we report nearby genes with the highest likelihood of linkage to ME/CFS. We also investigated whether the linkage of these regions changed when we further compared groups based on sex or socioeconomic status, but no conclusive results were found. Comparison with the larger DecodeME study showed no overlapping results.
Comment from Prof Chris Ponting:
New ME/CFS genetics preprint from the Beentjes/ Khamseh/ Ponting groups
NB: Not DecodeME
We discover 7 genetic associations to ME/CFS that are independently replicated in UK Biobank and/or All of Us
ME/CFS case/control status required multiple lines of evidence
We used TarGene to minimise estimation bias. One replicated association is near the CLYBL gene, but is not its null allele
These results are not seen in DecodeME. Perhaps this reflects (i) how & when those in biobanks vs DecodeME were diagnosed & (ii) severity differences
Happy to hear feedback. Great work done by Joshua Slaughter as part of his Uni of Edinburgh PhD, and others.
Professor Chris Ponting, BlueSky
Other information relating to DecodeME
- The ME Association: Decode ME release initial DNA results! | August 7, 2025
- Edinburgh University: DecodeME
- Edinburgh University: Sequence ME
- Action for ME: Sequence ME & Long Covid
- The ME Association: Research: A large international study on Fibromyalgia has identified potential risk factors across patients’ genes | July 30, 2026