Chronic fatigue syndrome seems to have a very strong genetic element

We are beginning to understand the role that genetics plays at the beginning chronic fatigue syndromeor myalgic encephalomyelitis (ME/CFS). According to the largest study of its kind to date, more than 250 genes are involved. six times more than was detected earlier this year. Not only could this help us develop treatments that eliminate ME/CFS at the root, but the research will add to our knowledge of how it differs from long Covid, a very similar condition.

“This opens up a huge number of new opportunities for both developing new treatments and repurposing drugs,” says a team member. Steve Gardner at Precision Life in Oxford.

ME/CFS is a chronic disease that is often disabling. It has many symptoms, but the main feature is post-exertional malaise, in which even mild activity leads to prolonged exhaustion. ME/CFS usually caused by infectionbut it is unclear why many people can contract such an infection but not develop the disease.

To learn more, Gardner's team looked at genomic data from more than 10,500 people who had been diagnosed with ME/CFS. The data was previously collected by a project called DecodeME, which in August showed that people with ME/CFS have key genetic differences from people without the condition.

Now Gardner and his colleagues have compared these data with data from people without ME/CFS from the UK Biobank. They focused on genetic variants called single nucleotide polymorphisms (SNPs), in which one letter of the genome changes.

A standard analysis would look at one SNP at a time, but “the biology of complex diseases is not like that at all,” Gardner says. “There are a lot of genes involved and they interact with each other. Some enhance each other's effects, some suppress each other's effects.”

Instead, the researchers looked for clusters of SNPs associated with ME/CFS risk. They found 22,411 such groups, consisting of combinations of 7,555 SNPs, out of more than 300,000 they identified overall. The researchers also found that the more of these SNP groups a person has, the more likely they are to develop ME/CFS.

“This is where they start to push things forward,” says Jacqueline Cliff at Brunel University London.

The team then mapped SNPs to 2,311 genes, each of which plays a small role in a person's risk. From these, they identified 259 “core” genes that showed the strongest associations with ME/CFS and had the most common SNPs. This represents a big improvement on the August study, which found 43 genes.

“If you are truly interested in drug opportunities and want to benefit as many patients as possible, [variants] Obviously, with a higher prevalence and a higher effect, you would choose to study first,” says Gardner. There are currently no specific medications to treat ME/CFS, but people may be offered painkillers or antidepressants and taught how to manage their energy.

Danny Altmann at Imperial College London hopes research like this will shed light on the serious harms of ME/CFS, which he says have been misunderstood and ignored for decades. “We are coming of age in terms of genomics and pathophysiology.”

Some studies have previously attempted to identify genetic risk factors for ME/CFS. “Some repeated [each other’s findings] and some don’t,” Altmann says. “It’s all about scale and power.” Studies with too few participants are likely to miss true genetic signals.

In August, DecodeME researchers also identified variants in eight genomic regions, including 43 genes, that contribute to ME/CFS risk, but they were unable to replicate them all in independent data sets. However, PrecisionLife rediscovered all eight regions, confirming the idea that they are the true risk factors for this disease.

ME/CFS is also often compared to long Covid, which is similarly caused by infection and also typically results in post-exertional malaise. In a new study, researchers attempted to clarify the relationship between these conditions by comparing the list of genes they linked to ME/CFS with those that have been linked to ME/CFS. they have previously been associated with long Covid. “About 42 percent of the genes we found in long Covid are also reproducibly found in multiple cohorts of ME patients,” Gardner says. “Clearly these are two overlapping diseases.”

But we can't be too sure long covid The results, Cliff says, are because these people were analyzed differently than people with ME/CFS. In the paper, the researchers say the genetic overlap they identified is a “minimum estimate,” suggesting the conditions may be more genetically similar than we think.

Altmann and his colleague Rosemary Boytonalso at Imperial, just now received £1.1 million in funding to find out how ME/CFS and long Covid are linked. Altmann says they're aiming to recruit people with both diseases and do “a really high-tech, high-resolution analysis,” including immune systemany hidden viruses lingering in their bodies and their gut microbiomes – they were all complicit in these conditions.

By understanding the mechanisms underlying ME/CFS and long-term coronavirus, and understanding how they vary from person to person, we hope to be able to directly target them, says Altmann.