SynthesisAnnals of neurology2023
Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor.
Open access · hybridAbstract readMeta-Analysis
In one paragraph
Synthesis in Annals of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 3 pooled it
12.9field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.The journal of headache and pain · 2026Pooled it
- Risk factors associated to disability in primary headaches: a systematic review to inform future iterations of the Global Burden of Disease Study.The journal of headache and pain · 2025Pooled it
- Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses.Frontiers in neurology · 2024Pooled it
- The Prevalence and Incidence of Cluster Headache: A Norwegian Population-Based Time-Trend Study.Neurology · 2026Article
- Shared genetic architecture between depression and migraine: a large-scale genome-wide cross-trait analysis.The journal of headache and pain · 2026Article
- Sex differences in cluster headache: insights from the Chinese Cluster Headache Register Individual Study (CHRIS).The journal of headache and pain · 2026Observational
- Smoking and cluster headache: clinical, gender, and treatment insights from a cross-sectional cluster analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Risk and reward seeking behaviour in episodic cluster headache - a psychometric and behavioural study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- The emerging role of epigenetic regulation in pain sensitization associated with headache disorders.The journal of headache and pain · 2025Review
- Hallmarks of primary headache: part 3 - cluster headache.The journal of headache and pain · 2025Review
- Reviewing the complex relationship between circadian rhythms and cluster headache.Cephalalgia : an international journal of headache · 2025Review
- Article
- Exploration of Prolonged Remission and the Natural Course of Cluster Headache: An Interview-Based Cohort Study.Neurology · 2025Article
- Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study.Annals of neurology · 2025Article
- 15. Cluster Headache.Pain practice : the official journal of World Institute of Pain · 2025Review
- Cluster Headache and Migraine Shared and Unique Insights: Neurophysiological Implications, Neuroimaging, and Biomarkers: A Comprehensive Review.Journal of clinical medicine · 2025Review
- Uncovering drug targets for cluster headache through proteome-wide Mendelian randomization analysis.The journal of headache and pain · 2025Article
- Article
- Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications.Neurology international · 2024Review
- Acute and preventive medical treatment of cluster headache in Taiwan: A narrative review.Journal of the Chinese Medical Association : JCMA · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
95 authors at 20 institutions in 15 countries.
Bendik S WinsvoldDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.ORCID 0000-0003-4171-8919
Aster V E HarderDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-5477-7232
Caroline RanCentre for Cluster Headache, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Mona A ChalmerDepartment of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen University Hospital, Glostrup, Denmark.
Maria Carolina DalmassoDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Egil FerkingstaddeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Kumar Parijat TripathiDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry, Uniklinik Köln, Cologne, Germany.
Elena BacchelliDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Sigrid BørteDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
Carmen FourierCentre for Cluster Headache, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6618-8948
Anja S PetersenDepartment of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen University Hospital, Glostrup, Denmark.
Lisanne S VijfhuizenDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Sigurdur H MagnussondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Emer O'ConnorDepartment of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
Gyda BjornsdottirdeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Paavo HäppöläInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Yen-Feng WangDepartment of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.ORCID 0000-0001-7027-3432
Ida CallesenDepartment of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen University Hospital, Glostrup, Denmark.
Tim KeldermanDepartment of Neurology, Ghent University Hospital, Ghent, Belgium.
Victor J GallardoHeadache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Departament de Medicina, Universitat Autònoma de Barcelona, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Irene de BoerDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-7261-762X
Felicia Jennysdotter OlofsgårdCentre for Cluster Headache, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Katja HeinzeKiel Migraine and Headache Centre, Kiel, Germany.
Nunu LundDepartment of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen University Hospital, Glostrup, Denmark.
Laurent F ThomasK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.ORCID 0000-0003-0548-2486
Chia-Lin HsuInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Matti PirinenInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Heidi HautakangasInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Marta RibasésPsychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Universitat Autònoma de Barcelona, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Simona GuerzoniAOU Policlinico Modena, Modena University Hospital, Modena, Italy.
Prasanth SivakumarDepartment of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
Janice YipDepartment of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
Axel HeinzeKiel Migraine and Headache Centre, Kiel, Germany.
Fahri KüçükaliComplex Genetics of Alzheimer's Disease Group, Center for Molecular Neurology, VIB, Antwerp, Belgium.
Sisse R OstrowskiDepartment of Clinical Immunology, Centre of Diagnostic Investigation, Rigshospitalet, Copenhagen, Denmark.
Ole B PedersenDepartment of Clinical Immunology, Zealand University Hospital, Køge, Denmark.
Espen S KristoffersenDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.ORCID 0000-0002-8999-5424
Amy E MartinsenDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
María S ArtigasPsychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Universitat Autònoma de Barcelona, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Susie LagrataHeadache and Facial Pain Group, University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
Maria Michela CainazzoAOU Policlinico Modena, Modena University Hospital, Modena, Italy.
Joycee AdebimpeDepartment of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
Olivia QuinnDepartment of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
Carl GöbelKiel Migraine and Headache Centre, Kiel, Germany.
Anna CirkelKiel Migraine and Headache Centre, Kiel, Germany.
Alexander E VolkInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Stefanie Heilmann-HeimbachInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Anne Heidi SkogholtK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Maiken E GabrielsenK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Leopoldine A WilbrinkDepartment of Neurology, Zuyderland Hospital, Heerlen, The Netherlands.
Daisuke DannoHeadache and Facial Pain Group, University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
Dwij MehtaHeadache and Facial Pain Group, University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
Daníel F GuðbjartssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
HUNT All-In Headache, The International Headache Genetics Consortium, DBDS Genomic Consortium
Frits R RosendaalDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Ko Willems van DijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Rolf FronczekDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Michael WagnerDepartment of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
Martin SchererDepartment of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hartmut GöbelKiel Migraine and Headache Centre, Kiel, Germany.
Kristel SleegersComplex Genetics of Alzheimer's Disease Group, Center for Molecular Neurology, VIB, Antwerp, Belgium.
Olafur A SveinssonFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Luca PaniDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Michele ZoliDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Josep A Ramos-QuirogaPsychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Universitat Autònoma de Barcelona, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Efthimios DardiotisDepartment of Neurology, Faculty of Medicine, University of Thessaly, Volos, Greece.
Anna SteinbergDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Steffi Riedel-HellerInstitute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.
Christina SjöstrandDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Thorgeir E ThorgeirssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Hreinn StefanssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Laura SouthgateMolecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK.ORCID 0000-0002-2090-1450
Richard C TrembathDepartment of Medical & Molecular Genetics, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Jana VandrovcovaDepartment of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Koen PaemeleireDepartment of Neurology, Ghent University Hospital, Ghent, Belgium.
Kari StefanssondeCODE genetics/Amgen Inc., Reykjavik, Iceland.
Cathy Shen-Jang FannInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Elisabet WaldenlindDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Erling TronvikNorwegian Centre for Headache Research (NorHEAD), Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Rigmor H JensenDepartment of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen University Hospital, Glostrup, Denmark.
Shih-Pin ChenBrain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.ORCID 0000-0003-3492-9902
Henry HouldenDepartment of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
Gisela M TerwindtDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Christian KubischInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Elena MaestriniDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Michail VikelisGlyfada Headache Center, Glyfada, Greece.
Patricia Pozo-RosichHeadache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Departament de Medicina, Universitat Autònoma de Barcelona, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Andrea C BelinCentre for Cluster Headache, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6668-3172
Manjit MatharuHeadache and Facial Pain Group, University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
Arn M J M van den MaagdenbergDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Thomas F HansenDepartment of Neurology, Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen University Hospital, Glostrup, Denmark.
Alfredo RamirezDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID 0000-0003-4991-763X
John-Anker ZwartDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.ORCID 0000-0001-5721-0154
International Consortium for Cluster Headache Genetics
Leiden University Medical Center · NLdeCODE Genetics (Iceland) · ISUniversity College London · GBUniversity of Copenhagen · DKOslo University Hospital · NOUniversitat Autònoma de Barcelona · ESKarolinska Institutet · SENational Hospital for Neurology and Neurosurgery · GBNorwegian University of Science and Technology · NOClinical Research Center Kiel · DEUniversität Hamburg · DEAzienda Ospedaliero-Universitaria di Modena · ITGhent University Hospital · BEInstitute of Biomedical Sciences, Academia Sinica · TWKarolinska University Hospital · SENational Yang Ming Chiao Tung University · TWUniversity Hospital Schleswig-Holstein · DEUniversity of Antwerp · BEUniversity of Bologna · ITUniversity of Helsinki · FI
Funding
Wellcome TrustWellcome Trust 076113Wellcome Trust 085475Wellcome Trust 090355
Abstract
objectiveThe objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights.
methodsA total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses.
resultsThe estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine.
interpretationThis first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713-726.
Indexed as
Cluster HeadacheMigraine DisordersFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideRisk FactorsSmoking
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What Socratic holds
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.