| Title: | The genetic architecture of fibromyalgia across 2.5 million individuals |
| Journal: | Nature Medicine |
| Published: | 28 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42521817/ |
| DOI: | https://doi.org/10.1038/s41591-026-04492-6 |
| URL: | https://www.nature.com/articles/s41591-026-04492-6.pdf |
Publication 21269
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Abstract
Fibromyalgia is a common and debilitating chronic pain syndrome of poorly understood etiology. Here we conduct a multi-ancestry genome-wide association study meta-analysis across 2,563,755 individuals (54,629 cases and 2,509,126 controls) from 11 cohorts, identifying 26 risk loci for fibromyalgia. The strongest association was with a coding variant in HTT, the causal gene for Huntington's disease. Gene prioritization implicated the HTT regulator GPR52, as well as diverse genes with neural roles, including DCC, DRD2/NCAM1, MDGA2 and CELF4. Fibromyalgia heritability was exclusively enriched within brain tissues and neural cell types. Fibromyalgia showed strong, positive genetic correlation with a wide range of chronic pain, psychiatric and somatic disorders, including genetic correlations above 0.7 with low back pain, post-traumatic stress disorder and irritable bowel syndrome. Despite large sex differences in fibromyalgia prevalence, the genetic architecture of fibromyalgia was nearly identical between males and females. This study provides robust genetic evidence defining fibromyalgia as a central nervous system disorder, thereby establishing a biological framework for its complex pathophysiology and extensive clinical comorbidities.</p>
8 Keywords
- Female
- Fibromyalgia
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Polymorphism, Single Nucleotide
- Stress Disorders, Post-Traumatic
53 Authors
- Isabel Kerrebijn
- Gyda Bjornsdottir
- Keon Arbabi
- Lea Urpa
- Hele Haapaniemi
- Gudmar Thorleifsson
- Lilja Stefansdottir
- Stephan Frangakis
- Jesse Valliere
- Lovemore Kunorozva
- Erik Abner
- Caleb Ji
- Markus Kangur
- Bitten Aagaard
- Henning Bliddal
- Søren Brunak
- Mie T. Bruun
- Maria Didriksen
- Christian Erikstrup
- Sarah Finer
- Arni J. Geirsson
- Daniel F. Gudbjartsson
- Thomas F. Hansen
- David van Heel
- Ingileif Jonsdottir
- Stacey Knight
- Kirk U. Knowlton
- Christina Mikkelsen
- Lincoln D. Nadauld
- Thorunn A. Olafsdottir
- Sisse R. Ostrowski
- Ole B. V. Pedersen
- Saedis Saevarsdottir
- Astros T. Skuladottir
- Erik Sørensen
- Hreinn Stefansson
- Patrick Sulem
- Olafur A. Sveinsson
- Gudny E. Thorlacius
- Unnur Thorsteinsdottir
- Henrik Ullum
- Arnor Vikingsson
- Thomas M. Werge
- Richa Saxena
- Kari Stefansson
- Chad M. Brummett
- Bente Glintborg
- Daniel J. Clauw
- Thorgeir E. Thorgeirsson
- Frances M. K. Williams
- Nasa Sinnott-Armstrong
- Hanna M. Ollila
- Michael Wainberg
1 Application
| Application ID | Title |
|---|---|
| 116200 | Influences of rare non-protein-coding genetic variants across the phenome |
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