Genetic study provides strongest evidence yet supporting neurologic basis of fibromyalgia

Clinical takeaway: Fibromyalgia should continue to be managed as a biologically based chronic pain disorder. Although these findings do not change diagnosis or treatment today, they strengthen the rationale for explaining the condition as one of altered pain processing rather than primarily autoimmune or psychological, while pointing toward future targeted therapies.

Fibromyalgia has long been a source of clinical uncertainty, with ongoing debate about whether it is primarily neurologic, autoimmune, or psychological in origin. The largest genetic study of the disorder to date provides strong evidence that fibromyalgia is fundamentally a disorder of the nervous system, offering new biologic insights that could eventually guide more targeted treatments.

Researchers analyzed genetic data from more than 2.5 million individuals, including 54,629 people with fibromyalgia, and identified 26 genetic loci associated with disease risk. Many of the implicated genes are involved in brain and nerve function, supporting the concept that fibromyalgia is primarily a disorder of altered pain processing. Heritability was enriched almost exclusively in brain tissues and neuronal cell types, with little evidence supporting a primary autoimmune mechanism.

The strongest genetic association involved HTT, the gene responsible for Huntington disease. Although the fibromyalgia-associated variant is distinct from the mutation that causes Huntington disease, the finding—and a second association involving the HTT regulator GPR52—raises the possibility that pathways already under investigation for Huntington disease could eventually be explored as therapeutic targets for fibromyalgia.

The study also found substantial genetic overlap between fibromyalgia and other chronic pain conditions, including low back pain and irritable bowel syndrome, as well as post-traumatic stress disorder, supporting the concept that shared nervous system mechanisms may underlie these commonly coexisting disorders. Despite fibromyalgia being diagnosed much more often in women, investigators found no meaningful differences in genetic risk between the sexes, suggesting that non-genetic factors likely account for the disparity.

"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," said Michael Wainberg, PhD, co-senior author and investigator at the Lunenfeld-Tanenbaum Research Institute and the University of Toronto.

Source: Kerrebijn I, et al. (2026 July 28) Nat Med. The genetic architecture of fibromyalgia across 2.5 million individuals