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The government has invested £4.75 million in a genomic sequencing programme aimed at identifying the biological causes of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), in what researchers describe as the most detailed genetic study of the condition yet undertaken.

The SequenceME programme will sequence the complete genomes of up to 6000 patient samples, with the aim of producing a high-resolution genetic map of the condition and opening the way for better diagnostics and new treatments.

SequenceME will use long-read whole-genome sequencing, a technique that reads a person’s complete DNA sequence. This is a more advanced and informative approach than the short-read methods typically used in large studies and allows researchers to locate genes with much greater accuracy and to identify new biological mechanisms. It also enables detection of rare genetic changes that are difficult to see with other techniques; identification of structural variations, such as missing, duplicated, or rearranged sections of DNA; and identification of the epigenome in people with ME.

The research will involve a partnership between the University of Edinburgh, genome-sequencing company Oxford Nanopore Technologies, the European Molecular Biology Laboratory’s European Bioinformatics Institute, and Action for ME.

Immune and Nervous System Genes

ME/CFS causes debilitating fatigue, sleep difficulties, and cognitive impairment. There are around 390,000 people with the condition in the UK. Around one quarter of those with diagnosed disease are severely affected, leaving them housebound or unable to work. In most cases, it starts after an infection. There is limited understanding of the causes and biological mechanisms driving the condition, and it has no effective treatments. 

The SequenceME study builds on the DecodeME study, which established the world’s largest and most deeply characterised ME/CFS research cohort and laid the scientific foundations for large-scale genomic analysis.

DecodeME analysed the DNA of 15,579 people with ME, examining the one million locations on the genome where DNA changes are common. 

Last August, DecodeME researchers reported that ME/CFS is partly caused by genes related to the immune and nervous systems, which they said provided the “first robust evidence” that genes contributed to a person's chance of developing the disease.

The study found eight areas of genetic code that are different in people with ME/CFS than in healthy volunteers. Two of the most likely genes produced proteins that responded to an infection. Another likely gene is related to chronic pain.

Unprecedented Dataset 

The SequenceME programme will deliver a dataset “unlike anything previously available anywhere in the world,” said Sonya Chowdhury, chief executive of Action for ME, in a press release. She acknowledged funding from the Department of Health and Social Care and the charity’s partners and donors.

“Building on the findings from DecodeME, SequenceME should provide a better understanding of the underlying disease process,” said Dr Charles Shepherd, honorary medical adviser to the ME Association, in a press release, “in particular how the immune and nervous systems respond to a triggering infection in ME/CFS.” 

“For people with ME/CFS there is now real hope that we have a route to finding a much-needed diagnostic biomarker blood test and effective forms of treatment,” Shepherd said.

Deep sequencing using long-read technology “will allow us to pinpoint individual genes disrupted in ME/CFS, moving beyond broader chromosomal signals identified to date,” said Professor Chris Ponting, DecodeME investigator at the University of Edinburgh.

Ponting said the study also offered the potential to uncover patterns of familial inheritance and bring the field closer to more precise diagnosis and targeted treatments.

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.