Genetic Study Suggests Central Nervous System Role in Fibromyalgia
KEY TAKEAWAYS
- A genome-wide association study of more than 2.5 million individuals identified 26 risk loci associated with fibromyalgia.
- Fibromyalgia heritability was enriched in brain tissues and neural cell types, supporting a central nervous system contribution to the disorder.
- The strongest association involved a coding variant in HTT, although this variant is distinct from the rare repeat expansion that causes Huntington disease.
A large multi-ancestry genome-wide association study identified 26 genetic risk loci for fibromyalgia, providing evidence that the disorder has a biologic basis rooted largely in the nervous system, according to findings published in Nature Medicine.
Investigators analyzed genetic data from 2,563,755 individuals across 11 cohorts, including 54,629 people with fibromyalgia and 2,509,126 controls. Fibromyalgia cases were defined by ICD-10 code M79.7 in inpatient or primary care records.
Genetic Findings
- The strongest association was with rs149109767-A, a coding variant in HTT, the gene associated with Huntington disease. The fibromyalgia-associated variant was located far from the repeat-expansion region that causes Huntington disease.
- Additional prioritized genes included GPR52, DCC, DRD2/NCAM1, MDGA2, and CELF4, several of which have roles in neural development, synaptic function, or pain processing.
- Heritability enrichment was identified in brain regions including the cortex, caudate, frontal cortex, putamen, and anterior cingulate cortex.
- Genetic overlap was observed with chronic pain, psychiatric, and somatic conditions, including low back pain, posttraumatic stress disorder, and irritable bowel syndrome.
Despite the higher prevalence of fibromyalgia among women, investigators found largely similar genetic architecture between males and females. The authors also reported comparatively modest genetic correlations with autoimmune disorders and no major histocompatibility complex signal, suggesting fibromyalgia may not be primarily autoimmune, although peripheral immune or neuroimmune contributions remain possible.
According to the authors, limitations in the study include the predominance of European-ancestry participants and reliance on ICD codes, which may introduce diagnostic heterogeneity.
Source
Fred Hutch Cancer Center. Largest-ever genetic study of fibromyalgia points to a neurological origin of disorder and opens the door to new treatments. News release. Published July 28, 2026. Accessed July 30, 2026. https://www.fredhutch.org/en/news/releases/2026/07/largest-genetic-study-fibromyalgia.html
Kerrebijn I, Bjornsdottir G, Arbabi K, et al. The genetic architecture of fibromyalgia across 2.5 million individuals. Nat Med. Published online 2026. doi:10.1038/s41591-026-04492-6