Genetic risk factors of fibromyalgia identified in largest study of its kind

New genetic risk factors have been identified for fibromyalgia syndrome in a landmark study that involved scientists at King’s College London. The study, published in Nature Medicine, highlights how the nervous system plays an important role in the development of the disorder.

Fibromyalgia is characterized by widespread pain and tenderness, fatigue, and problems with sleep, memory and mood. Despite affecting about 2% of the global population, its biological causes have remained unclear. The results of this study are an important step toward resolving that uncertainty.

The team analyzed genetic data from more than 2.5 million adults, of whom 55,000 had been diagnosed with fibromyalgia. The researchers scanned millions of genetic differences across the DNA of people with and without fibromyalgia to find changes that were more common in those with the condition.

This enabled them to identify DNA sequence variants in 26 regions of the genome that affect the risk of developing fibromyalgia. Many of the genes implicated in these regions are involved in brain and nerve function.

Evidence from a vast dataset

Frances Williams, co-senior author of the paper and professor of genomic epidemiology at King’s College London, played an important role in bringing together data from 11 health research studies in the U.S., UK, Finland, Estonia, Denmark and Iceland, and 53 researchers across seven countries.

Williams said, “By studying the DNA of over 2 million individuals, we can be confident that the findings are real, and they suggest that fibromyalgia represents a problem in pain processing.”

Dr. Michael Wainberg, an investigator at the Lunenfeld-Tanenbaum Research Institute and the University of Toronto and co-senior author of the paper, said, “This work changes how we think about fibromyalgia at a fundamental level. For decades, patients have been dismissed or told their pain is simply psychological. Our findings confirm the condition has a clear biological basis.”

While the findings do not yet provide a genetic test for diagnosing fibromyalgia or a new treatment for patients, they offer valuable insights into the underlying biology of the condition. This could help researchers develop better ways to identify, understand and treat fibromyalgia in the future.

A surprising link to Huntington’s disease

Of the 26 genetic variants identified, the one most strongly linked to fibromyalgia risk was within the gene HTT. Different mutations in this gene cause Huntington’s disease, a severe, progressive and fatal neurodegenerative disorder. Another variant pointed to a receptor called GPR52 that regulates HTT levels. This receptor is already being investigated as a possible drug target in Huntington’s disease.

Williams helped interpret how the genetic findings relate to symptoms and conditions doctors commonly see in patients. The study revealed substantial genetic overlap between fibromyalgia and a range of other conditions, including low back pain, irritable bowel syndrome and post-traumatic stress disorder. The researchers think shared biological mechanisms within the nervous system may make people susceptible to several of these conditions, explaining why they often appear together.

Williams said, “We know that chronic pain syndromes cluster together in individuals and families and are genetically similar. Targeting the shared mechanisms underlying them could potentially benefit a whole cluster of disorders.”

Genes alone are not enough

Genetics are not the only determinant of whether someone develops fibromyalgia. The authors suspect that even people carrying many fibromyalgia genetic variants require other risk factors, such as a painful arthritic condition, to trigger fibromyalgia syndrome.

Dr. Nasa Sinnott-Armstrong, assistant professor at Fred Hutch Cancer Center and co-senior author of the paper, said, “Understanding how genes, environmental exposures, and life events jointly contribute to the risk of fibromyalgia syndrome is critical. Further research into triggers of fibromyalgia and corresponding changes in neural tissues will help understand what drives fibromyalgia and how to treat it.”

The study’s researchers founded the Chronic Pain Genomics Consortium to investigate other chronic pain syndromes, starting with pelvic pain. The consortium sees fibromyalgia as only the beginning of a broader exploration of the landscape of chronic pain conditions.

Williams said, “This study provides important new insights into why some people develop fibromyalgia syndrome and identifies biological pathways that could lead to new treatment approaches. One of these pathways is already the focus of drug trials for Huntington’s disease, raising the possibility that existing pharmaceutical research could eventually benefit people with fibromyalgia.

“The findings also help us better understand why fibromyalgia so often occurs alongside conditions such as anxiety and depression, bringing us closer to understanding the condition as a whole.”

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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