New chronic fatigue research reveals subtle genetic differences
Dr Katherine Huang and colleagues’ new study draws on UK Biobank data to show how subtle genetic differences can combine to create metabolic bottlenecks – and that makes some people vulnerable to chronic fatigue syndrome.
Millions of people worldwide live with Myalgic Encephalomyeltis/Chronic fatigue syndrome (ME/CFS), a condition that has long been misunderstood, underdiagnosed, and stigmatised. The COVID-19 pandemic dramatically increased the number of people experiencing post-infectious illnesses, including Long COVID, many of which share striking similarities with ME/CFS.
For decades, patients have been told their symptoms are “all in their head”. But just-published research in iScience journal shows how subtle genetic differences can converge to disrupt metabolism and stress-response pathways. That shift matters says lead author and Department of Biochemistry and Pharmacology researcher Dr Katherine Huang.
“When a condition is recognised as biological rather than psychological, patients are more likely to receive appropriate medical care, workplace accommodations, and social support.”
Using the UK Biobank, the research represents a milestone in understanding ME/CFS not as a single disease with a single cause, but as a complex condition shaped by genetics, metabolism and environmental triggers such as infection. That perspective opens the door to better diagnosis, targeted treatments, and earlier intervention for future generations, especially in the wake of COVID.
Dr Huang says the research confirms that ME/CFS is not caused by a single faulty gene. Instead, many small-effect genetic differences – seemingly insignificant on their own – may accumulate and strain key metabolic pathways to create something like a metabolic bottleneck.
Genetics, metabolism and the body’s stress response are tightly linked, she explains. “We identified genetic differences in pathways, involved in the HPA axis, cortisol regulation and stress response.”
“These pathways are connected to lipid and fat metabolism, including Very-Low-Density Lipoprotein, which plays a crucial role in energy transport.”
The researchers compared almost 900 patients with ME/CFS to over 36,000 people without, revealing a distinct biological profile that was specific to people with the condition. This new perspective enhances biological understanding and, it is hoped, strengthens the potential for finding effective therapies.