Large Scale Genetic Study on ME/CFS

Researchers have conducted the most extensive genetic analysis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition that can be lifelong and severely impact a person’s ability to exert themselves.

The DecodeME study recruited over 15,000 individuals of European descent diagnosed with the condition. It uncovered eight specific areas of the genome associated with ME/CFS, previously unlinked to the syndrome. Interestingly, the gene variants identified are also present in some healthy individuals. Yet, for those with ME/CFS, these variants likely interact with environmental factors, raising their risk for the disease, as suggested by the researchers.

Chris Ponting, a bioinformatician at the University of Edinburgh and co-author of the study, stated, “This provides the first solid evidence of genetic factors contributing to ME risk” during a news conference on August 6.

The findings have been shared as a preprint from the University of Edinburgh, though they haven’t yet undergone peer review.

Globally, estimates indicate that ME/CFS could impact around 67 million people. However, determining the precise prevalence is challenging, and research into its symptoms and treatments has been exceptionally slow. Partly, this is due to ongoing debates about what distinctly defines the core symptoms of the disease.

For several years, prominent psychiatrists have described ME/CFS as a psychological disorder. Discredited theories suggested that its symptoms—like brain fog, unrelieved fatigue, and chronic pain—were linked to patients’ mental states and insufficient exercise. These assumptions gained traction mainly because the limited clinical investigations couldn’t establish any biological changes linked to the syndrome.

According to the latest research, there is increasing evidence that ME/CFS has connections to issues within the nervous and immune systems.

Sonya Chowdhury, CEO of the charity Action for M.E. and another co-author of the study, remarked, “Our findings will lend credibility to the experiences of those suffering from ME.”

DecodeME utilized genome-wide association studies (GWAS) to examine genetic links to the condition. The study performed two GWAS analyses on about 15,600 individuals with ME/CFS, comparing their genomes with those of healthy individuals previously recorded in the UK Biobank, which includes data from 500,000 adults in the UK. These analyses pinpointed eight specific loci—locations in the genome—strongly associated with ME/CFS, marking genes that influence the condition’s risk.

Included in these findings are several genes related to immune function. Notably, the gene BTN2A2 has been linked in prior studies to how T cells operate, which play an essential role in combating infections. Another locus contained the CA10 gene, previously associated with pain—a connection that could help explain the heightened sensitivity to stimuli among ME/CFS patients.

These genetic associations do not indicate changes caused by the disease, but rather point to biological systems affecting individuals’ vulnerability to developing ME/CFS.

The researchers attempted to validate their findings by assessing whether the same genetic associations could be observed in 13,800 ME/CFS cases recorded in the UK Biobank and a similar study in the Netherlands. However, after statistical correction, they couldn’t replicate those associations.

Amy Mason, a research associate at the University of Cambridge who didn’t participate in the study, commented, “This might indicate inconsistencies in diagnosis data in those other datasets rather than flaws in the DecodeME findings.”

Meanwhile, Long COVID—a prolonged condition following a COVID-19 infection—shares several symptoms with ME/CFS. Nonetheless, DecodeME did not detect any of the same genetic signals found in a similarly sized GWAS analysis of long COVID published earlier this year, which leaves some uncertainty regarding the implications of those differences.

ME/CFS is notably biased by sex, with around 80% of patients being female. The DecodeME study did not uncover strong sex-related genetic links, and it was noted that the research did not investigate the X or Y chromosomes, where such effects might exist. Additionally, the focus on individuals of European descent could limit the applicability of these findings to other ethnic groups.

The authors are optimistic that DecodeME will serve as a foundation for future research, aiming to delve deeper into the genetic signals and explore the biological mechanisms suggested in ME/CFS. Currently, though, Ponting stated that these findings won’t immediately help in diagnostics or screening for the condition.

He emphasized, “There’s an urgent need for studies that target these regions to understand why each of these signals correlates with ME, so we can not only move but accelerate toward potential diagnostics and treatments.”