Largest Genetic Study of ME/CFS Identifies Risk Genes

A landmark study, DecodeME, has provided the first robust genetic evidence for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling illness marked by post-exertional malaise, chronic pain, and overwhelming fatigue.

The genome-wide association study (GWAS) analyzed DNA from 15,579 people with ME/CFS and 259,909 population controls of European ancestry. Researchers identified eight genome-wide significant genetic loci, including regions near RABGAP1L, BTN2A2, FBXL4, OLFM4, CA10, and ARFGEF2/CSE1L.

These genes are involved in infection response, mitochondrial function, immune regulation, and pain pathways.

One signal (near CA10) overlaps with genetic risk for chronic multi-site pain, while others (BTN2A2, OLFM4, RABGAP1L) are linked to immune responses against viruses and bacteria. Interestingly, no overlap was found with depression or anxiety, countering a long history of misdiagnosis.

These findings underscore that ME/CFS has both immunological and neurological roots, validating patients’ experiences after decades of dismissal.

While no diagnostic test or treatment exists yet, this study offers new biological targets for future therapies.

Funded by the UK’s Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR), DecodeME is now the world’s largest ME/CFS genetic study and a turning point for research.

Citation [pre-print]

Genetics Delivery Team, et al. (2025). Initial findings from the DECODEME genome-wide association study of Myalgic Encephalomyelitis/chronic fatigue syndrome. medRxiv. https://doi.org/10.1101/2025.08.06.25333109