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Record W4414345372 · doi:10.1101/2025.09.18.25335914

The genetic architecture of fibromyalgia across 2.5 million individuals

2025· preprint· en· W4414345372 on OpenAlexafffund
Isabel Kerrebijn, Gyða Björnsdóttir, Keon Arbabi, Lea Urpa, Hele Haapaniemi, Gudmar Thorleifsson, Lilja Stefánsdóttir, Stephan Frangakis, Jesse Valliere, Lovemore Kunorozva, Erik Abner, Chuanshu Ji, Bitten Aagaard, Henning Bliddal, Søren Brunak, Mie Topholm Bruun, Maria Didriksen, Christian Erikstrup, Árni Jón Geirsson, Daníel F. Guðbjartsson, Thomas Folkmann Hansen, Ingileif Jónsdóttir, Stacey Knight, Kirk U. Knowlton, Christina Mikkelsen, Lincoln Nadauld, Thorunn A. Olafsdottir, Sisse Rye Ostrowski, Ole Birger Pedersen, Saedís Saevarsdóttir, Ástrós Skúladóttir, Erik Sørensen, Hreinn Stefánsson, Patrick Sulem, Ólafur Sveinsson, Guðný Ella Thorlacius, Unnur Thorsteinsdottir, Henrik Ullum, Arnór Víkingsson, Thomas Werge, Richa Saxena, Kāri Stefánsson, Chad M. Brummett, Bente Glintborg, Daniel J. Clauw, Thorgeir E. Thorgeirsson, Frances M. K. Williams, Nasa Sinnott-Armstrong, Hanna M. Ollila, Michael Wainberg

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicFibromyalgia and Chronic Fatigue Syndrome Research
Canadian institutionsLunenfeld-Tanenbaum Research InstitutePublic Health OntarioUniversity of TorontoCentre for Addiction and Mental HealthMount Sinai Hospital
FundersNatural Sciences and Engineering Research Council of CanadaHORIZON EUROPE Framework ProgrammeVersus ArthritisHorizon 2020 Framework ProgrammeNovo Nordisk FondenNational Institutes of HealthEesti TeadusagentuurEuropean CommissionRigshospitaletParker Institute for Cancer ImmunotherapyMassachusetts General HospitalNovo NordiskGentofte HospitalCanadian Institutes of Health ResearchDanmarks Frie Forskningsfond
KeywordsFibromyalgiaIrritable bowel syndromeGenetic architectureChronic fatigue syndromeChronic painHeritabilityDiseaseGenetic association

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.008
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.021

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.008
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0010.002
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.325
Teacher spread0.304 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes2
Has abstractyes

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