Chronic Fatigue Syndrome May Have a Significant Genetic Influence.

Recent research is illuminating how genetics contributes to the development of chronic fatigue syndrome, also known as myalgic encephalomyelitis (ME/CFS). This latest study, the most extensive of its kind to date, identifies over 250 genes, significantly outpacing previous discoveries. The findings paves the way for targeted treatments for ME/CFS and enriches our understanding of how it varies from conditions like long COVID-19.

“We are exploring numerous possibilities, including new treatment options and repurposing existing medications,” remarks Steve Gardner of Precision Life in Oxford.

ME/CFS is a chronic and often debilitating illness characterized primarily by severe fatigue following even minor exertion. The cause is often linked to infections, yet not every individual exposed to these infections goes on to develop symptoms.

To deepen the understanding of this condition, Gardner’s team analyzed genomic information from over 10,500 individuals diagnosed with ME/CFS. This data originated from the DecodeME project, which notably found that patients with ME/CFS possess distinct genetic characteristics when compared to individuals without the disorder.

Subsequently, Gardner and colleagues cross-referenced this data with information from the UK Biobank, focusing on genetic variations known as single nucleotide polymorphisms (SNPs), which occur when one letter of the genetic code is altered.

While traditional analyses often evaluate one SNP at a time, Gardner notes, “The complexity of disease biology doesn’t operate that way. Multiple genes interact, with some enhancing and others diminishing each other’s effects.”

In a different approach, the researchers sought groups of SNPs linked to the risk of developing ME/CFS, uncovering 22,411 such groups drawn from 7,555 combinations of SNPs, out of an extensive dataset of over 300,000. They also discovered that individuals with a higher count of these SNP groups faced an increased likelihood of developing ME/CFS.

“This is where their progress begins,” adds Jacqueline Cliff from Brunel University, London.

The researchers proceeded to map the SNPs to 2,311 genes. Each gene plays a subtle role in an individual’s risk, culminating in the identification of 259 “core” genes that had a robust association with ME/CFS and contained the most frequently observed SNPs. This represents a profound advancement from the earlier August study, which identified only 43 genes.

“For drug discovery, it’s essential to focus on variants with greater prevalence and significant effect sizes,” Gardner states. While there are currently no specific medications for ME/CFS, symptomatic treatments like pain relievers and antidepressants may be offered, along with resources for energy management.

Danny Altman, a professor at Imperial College London, expresses optimism that investigations like this will highlight the severe impact of ME/CFS, a condition that has long been misunderstood. “We are gaining momentum in understanding genomics and pathophysiology.”

Previous studies have sought to pinpoint genetic risk factors for ME/CFS, but often duplicated findings. “It’s primarily about scale and statistical power,” explains Altman, emphasizing that inadequate sample sizes can overlook significant genetic signals.

In August, DecodeME researchers indicated several mutations in eight genomic regions, identifying 43 genes with links to ME/CFS risk, though not all could be validated in independent datasets. Nevertheless, PrecisionLife verified all eight regions, reinforcing their status as legitimate risk factors for the ailment.

ME/CFS is frequently compared to long COVID, given that both arise from infections and frequently result in post-exertional fatigue. In this recent study, researchers aimed to explore the connections between these conditions by analyzing gene lists associated with ME/CFS against those linked with long COVID-19. “Approximately 42 percent of the genes identified in long COVID-19 have been demonstrated in multiple cohorts of ME,” Gardner observes, underscoring the partially overlapping nature of these two diseases.

Despite this, Cliff cautioned that differing analyses of long COVID patients limit researchers’ confidence in the outcomes. The authors indicate that their genetic overlap findings represent a “minimal estimate,” implying a greater genetic similarity than previously assumed between these conditions.

Altman and his colleagues, including Rosemary Boyton, have recently secured £1.1 million in funding to explore the potential links between ME/CFS and long COVID-19. The focus will be on recruiting individuals with both conditions to conduct a comprehensive analysis that includes an overview of participants’ health, the immune system, and aspects such as latent viruses within the body and gut microbiome, believed to be contributors to these symptoms.

By delving into the mechanisms behind ME/CFS and long COVID, as well as individual variations, Altman aspires to create tailored interventions.