Two large-scale genetic studies involving millions of participants have identified variants associated with fibromyalgia, supporting the role of central nervous system dysfunction in the chronic pain condition. The research highlights genes involved in neuronal function and brain-related issues. While promising, experts note the findings are preliminary and point to multifaceted causes.
Fibromyalgia affects 2 to 3 per cent of people, causing chronic pain throughout the body, but its causes remain unclear, complicating treatment. A leading hypothesis posits changes in how the central nervous system processes pain signals, possibly triggered by infections or gut microbiome alterations.
To explore genetic factors, researchers conducted genome-wide association studies focusing on single-letter DNA variations. The first study, led by Michael Wainberg at Mount Sinai Hospital in Toronto, Canada, analyzed 54,629 individuals with fibromyalgia—mostly of European ancestry—and 2,509,126 without the condition, drawing from cohorts in the US, UK, and Finland. It identified 26 genetic variants linked to higher fibromyalgia risk.
The second study, led by Joel Gelernter at Yale School of Medicine, examined 85,139 people with fibromyalgia and 1,642,433 controls from the US and UK, including European, Latin American, and African ancestries. This effort found 10 variants in the European group, one in the African group, and 12 cross-ancestry variants.
Wainberg and Gelernter declined interviews, as their studies are preprints not yet peer-reviewed (medRxiv DOIs: 10.1101/2025.09.18.25335914 and 10.1101/2025.09.18.25335991). The strongest association in Wainberg's study involved a variant in the huntingtin gene, which is also linked to Huntington's disease but through a different mechanism.
"Both studies, in terms of sample size, are really great," says Cindy Boer at Erasmus Medical Center in Rotterdam, the Netherlands. The variants point to neuronal roles in the brain, aligning with prior links to pain, post-traumatic stress disorder, and depression. Boer notes that fibromyalgia likely involves thousands of variants plus environmental factors like air pollution, requiring larger studies for full insight.
These findings reinforce brain tissue involvement, per Boer, and could guide future treatments targeting specific pathways, though such advances are years away. Current options like exercise, therapies, and antidepressants yield mixed results.
Alternative mechanisms persist: David Andersson at King’s College London has shown fibromyalgia antibodies cause pain hypersensitivity in mice, suggesting autoimmunity and peripheral nerve roles. "I am very confident in the conclusions from our own work on fibromyalgia, and certain that our published work will be the inflection point marking when the field changed focus from the central nervous system to autoantibodies and peripheral neuronal mechanisms," Andersson says. Boer's analysis indicates the new studies may have missed some variants due to strict statistical thresholds but do not negate autoimmune evidence, as some implicated genes tie to immune responses.
Overall, these studies represent first steps toward unraveling fibromyalgia's roots and potential therapies.