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Peer-reviewedCC BYNature Medicine

The genetic architecture of fibromyalgia across 2.5 million individuals

  • Isabel Kerrebijn1,2,3
  • Gyða Björnsdóttir4
  • Keon Arbabi1,5,2,3
  • Lea Urpa6,7,8,9
  • Hele Haapaniemi7
  • Guðmar Þorleifsson4
  • Lilja Stefánsdóttir4
  • Stephan G. Frangakis10,11
  • Jesse Tyler Valliere7,8,12
  • Lovemore Kunorozva6,13,7,14,12
  • Erik Abner15,16
  • Caleb Ji17,2,3
44 more authors
  • Markus Kangur2,18
  • Bitten Aagaard18,19
  • Henning Bliddal20,21
  • Søren Brunak21,22,23
  • Mie Topholm Bruun23,24
  • Maria Didriksen24,25
  • Christian Erikstrup25,26,27
  • Sarah Finer28,4
  • Árni J. Geirsson27,29
  • Daniel F. Gudbjartsson4
  • Thomas Folkmann Hansen30,31,32,33
  • David A. van Heel34,35,33
  • Ingileif Jónsdóttir4,24
  • Stacey Knight33,36
  • Kirk U. Knowlton33,4
  • Christina Mikkelsen24
  • Lincoln D. Nadauld36,37
  • Thorunn A. Olafsdottir4,38
  • Sisse Rye Ostrowski24,39,4
  • Ole Birger Pedersen37,39,24
  • Saedís Saevarsdóttir4,38
  • Ástrós Skúladóttir4,38
  • Erik Sørensen24,40
  • Hreinn Stefánsson4
  • Patrick Sulem4
  • Olafur Arni Sveinsson38
  • Guðný Ella Thorlacius4,27
  • Unnur Þorsteinsdóttir4
  • Henrik Ullum
  • Arnór Víkingsson27,4
  • Thomas M. Werge39
  • Frances M. K. Williams
  • FinnGen
  • David van Heel34,35
  • Richa Saxena6,13,14
  • Kāri Stefánsson4
  • Chad M. Brummett10
  • Bente Glintborg39
  • Daniel Joseph Clauw
  • Thorgeir E. Thorgeirsson4
  • Frances M. K. Williams
  • Nasa Sinnott-Armstrong
  • Hanna Maria Ollila
  • Michael Wainberg
40 affiliations
  1. 1Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
  2. 2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  3. 3Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
  4. 4Amgen deCODE Genetics, Reykjavik, Iceland
  5. 5Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  6. 6Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
  7. 7Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
  8. 8Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA
  9. 9Broad Institute, Stanley Center of Psychiatric Research, Cambridge, MA, USA
  10. 10Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA
  11. 11Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan
  12. 12Broad Institute, Molecular and Population Genetics Program, Cambridge, MA, USA
  13. 13Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA
  14. 14Molecular and Population Genetics Program, Broad Institute, Cambridge, MA, USA
  15. 15Institute of Genomics, Estonian Genome Center, University of Tartu, Tartu, Estonia
  16. 16Estonian Genome Center, University of Tartu, Tartu, Estonia
  17. 17Department of Computer Science, University of Toronto, Toronto, Ontario, Canada
  18. 18Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark
  19. 19The Parker Institute, Copenhagen University Hospital Bispebjerg Frederiksberg, Denmark
  20. 20The Parker Institute, Copenhagen University Hospital Bispebjerg Frederiksberg, Copenhagen, Denmark
  21. 21Department of Public Health, University of Copenhagen, Copenhagen, Denmark
  22. 22Novo Nordisk Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
  23. 23Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
  24. 24Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  25. 25Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
  26. 26Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  27. 27Department of Rheumatology, Landspitali University Hospital, Reykjavik, Iceland
  28. 28Wolfson Institute of Population Health, Queen Mary University of London, London, UK
  29. 29Neurogenomics, Translational Research Centre, Copenhagen University Hospital, Glostrup Denmark
  30. 30Danish Headache Center, Copenhagen University Hospital, Glostrup, Denmark
  31. 31Danish Multiple Sclerosis Center, Copenhagen University Hospital, Glostrup, Denmark
  32. 32Neurogenomics, Translational Research Centre, Copenhagen University Hospital, Glostrup, Denmark
  33. 33Intermountain Medical Center, Intermountain Heart Institute, Salt Lake City, UT, USA
  34. 34Blizard Institute, Queen Mary University of London, London, UK
  35. 35Precision Healthcare University Research Institute, Queen Mary University of London, London, UK
  36. 36Intermountain Healthcare, Saint George, UT, USA
  37. 37Department of Clinical Immunology, Zealand University Hospital, Koege, Denmark
  38. 38School of Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  39. 39Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  40. 40Department of Neurology, Landspitali University Hospital, 108 Reykjavik, Iceland
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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.

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Cite

BibTeXRIS
BibTeX
@article{kerrebijn2026genetic,
  title = {{The genetic architecture of fibromyalgia across 2.5 million individuals}},
  author = {Isabel Kerrebijn and Gyða Björnsdóttir and Keon Arbabi and Lea Urpa and Hele Haapaniemi and Guðmar Þorleifsson and Lilja Stefánsdóttir and Stephan G. Frangakis and Jesse Tyler Valliere and Lovemore Kunorozva and Erik Abner and Caleb Ji and Markus Kangur and Bitten Aagaard and Henning Bliddal and Søren Brunak and Mie Topholm Bruun and Maria Didriksen and Christian Erikstrup and Sarah Finer and Árni J. Geirsson and Daniel F. Gudbjartsson and Thomas Folkmann Hansen and David A. van Heel and Ingileif Jónsdóttir and Stacey Knight and Kirk U. Knowlton and Christina Mikkelsen and Lincoln D. Nadauld and Thorunn A. Olafsdottir and Sisse Rye Ostrowski and Ole Birger Pedersen and Saedís Saevarsdóttir and Ástrós Skúladóttir and Erik Sørensen and Hreinn Stefánsson and Patrick Sulem and Olafur Arni Sveinsson and Guðný Ella Thorlacius and Unnur Þorsteinsdóttir and Henrik Ullum and Arnór Víkingsson and Thomas M. Werge and Frances M. K. Williams and FinnGen and David van Heel and Richa Saxena and Kāri Stefánsson and Chad M. Brummett and Bente Glintborg and Daniel Joseph Clauw and Thorgeir E. Thorgeirsson and Frances M. K. Williams and Nasa Sinnott-Armstrong and Hanna Maria Ollila and Michael Wainberg},
  journal = {Nature Medicine},
  year = {2026},
  month = jul,
  doi = {10.1038/s41591-026-04492-6},
  url = {https://doi.org/10.1038/s41591-026-04492-6},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The genetic architecture of fibromyalgia across 2.5 million individuals
AU  - Isabel Kerrebijn
AU  - Gyða Björnsdóttir
AU  - Keon Arbabi
AU  - Lea Urpa
AU  - Hele Haapaniemi
AU  - Guðmar Þorleifsson
AU  - Lilja Stefánsdóttir
AU  - Stephan G. Frangakis
AU  - Jesse Tyler Valliere
AU  - Lovemore Kunorozva
AU  - Erik Abner
AU  - Caleb Ji
AU  - Markus Kangur
AU  - Bitten Aagaard
AU  - Henning Bliddal
AU  - Søren Brunak
AU  - Mie Topholm Bruun
AU  - Maria Didriksen
AU  - Christian Erikstrup
AU  - Sarah Finer
AU  - Árni J. Geirsson
AU  - Daniel F. Gudbjartsson
AU  - Thomas Folkmann Hansen
AU  - David A. van Heel
AU  - Ingileif Jónsdóttir
AU  - Stacey Knight
AU  - Kirk U. Knowlton
AU  - Christina Mikkelsen
AU  - Lincoln D. Nadauld
AU  - Thorunn A. Olafsdottir
AU  - Sisse Rye Ostrowski
AU  - Ole Birger Pedersen
AU  - Saedís Saevarsdóttir
AU  - Ástrós Skúladóttir
AU  - Erik Sørensen
AU  - Hreinn Stefánsson
AU  - Patrick Sulem
AU  - Olafur Arni Sveinsson
AU  - Guðný Ella Thorlacius
AU  - Unnur Þorsteinsdóttir
AU  - Henrik Ullum
AU  - Arnór Víkingsson
AU  - Thomas M. Werge
AU  - Frances M. K. Williams
AU  - FinnGen
AU  - David van Heel
AU  - Richa Saxena
AU  - Kāri Stefánsson
AU  - Chad M. Brummett
AU  - Bente Glintborg
AU  - Daniel Joseph Clauw
AU  - Thorgeir E. Thorgeirsson
AU  - Frances M. K. Williams
AU  - Nasa Sinnott-Armstrong
AU  - Hanna Maria Ollila
AU  - Michael Wainberg
PY  - 2026
DA  - 2026/07/28
JO  - Nature Medicine
DO  - 10.1038/s41591-026-04492-6
UR  - https://doi.org/10.1038/s41591-026-04492-6
AB  - 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.
SN  - 1078-8956
SN  - 1546-170X
SN  - 1744-7933
ER  -