Key genetic differences found in people with chronic fatigue syndrome

Genetic factors that could contribute to people’s risk of developing chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), have been identified in a large study. Scientists have linked eight regions of the human genome to the condition, based on DNA samples from more than 15,000 people who have it.

“Our study provides the first robust evidence of genetic contributions to ME,” says Sonya Chowdhury at the charity Action for ME in the UK.

In the long run, the findings could contribute to the development of new diagnostic tools and treatments for ME/CFS, which has been recognised for decades and is marked chiefly by post-exertional malaise, a severe and debilitating response to even mild exertion.

But already, the results provide “validity and credibility” for people with the condition, says Chowdhury. “Many people have experienced comments like ‘ME’s not real’,” she says. “They’ve been to doctors and been disbelieved and told it’s not a real illness.”

“This will be huge for the patient population,” says Andy Devereux-Cooke, co-founder of the Science for ME forum, who has had the condition for 45 years.

The study, called DecodeME, compared DNA samples from just over 15,500 people with ME/CFS and nearly 260,000 without it, all of whom were from the UK and of European ancestry.

“We have found eight genetic signals,” says Chris Ponting at the University of Edinburgh in the UK. The eight genome regions involved look significantly different in people with ME/CFS, indicating that genetic variants there contribute to the risk of developing it. The University of Edinburgh announced the findings in a press briefing, but they haven’t yet been published in a journal or on a pre-print server.

Within these eight regions, the team identified 43 protein-coding genes, of which 29 looked especially promising. “When we dig down into these eight different genetic signals, we find genes that are related to both the immune system and the nervous system,” says Ponting. “Overall, the activities of the genes in these signals are enriched in the brain’s tissues. They are more likely to be active in the brain than elsewhere, pointing to a nervous system involvement.”

The researchers also identified an immune system-related gene called RABGAP1L as a probable contributor to ME/CFS risk. This fits with the testimony of most people with the condition, who say that an initial infection, which often seemed mild, preceded the onset of their symptoms.

“My thought has always been that there is something different about the immune system in people with ME/CFS,” says Jackie Cliff at Brunel University of London, who adds that the study is “a good jump forward in ME/CFS research”.

The work didn’t find any differences in genetic risk between men and women, even though ME/CFS is much more common in women. However, the team hasn’t yet analysed the X and Y sex chromosomes.

The next step is to study the eight regions of the genome that have been highlighted in more detail, to try to figure out how the genetic alterations are translated into molecular and cellular processes in people with and without ME/CFS. This might one day lead to diagnostic tests and drug treatments that target the core mechanisms of the condition. However, it will only happen if research funders support it. “There’s an absolute dearth of funding,” says Cliff.

The harms caused by ME/CFS are considerable, with an estimated 67 million people affected by it worldwide. A 2017 report by the think tank 20/20health estimated that it costs the UK economy £3.3 billion per year in healthcare and lost productivity. “It is a forgotten and forsaken disease and one, therefore, that deserves a lot of people’s attention and investment,” says Ponting.