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Record W2099661900 · doi:10.1212/wnl.0000000000001606

Shared genetic basis for migraine and ischemic stroke

2015· review· en· W2099661900 on OpenAlexfundno aff
Rainer Malik, Tobias Freilinger, Bendik S. Winsvold, Verneri Anttila, Jason Vander Heiden, Matthew Traylor, Boukje de Vries, Gisela M. Terwindt, Jonathan Sturm, Joshua C. Bis, Jemma C. Hopewell, Michel D. Ferrari, Kristiina Rannikmäe, Maija Wessman, Mikko Kallela, Christian Kubisch, Myriam Fornage, James F. Meschia, Terho Lehtimäki, Cathie Sudlow, Robert Clarke, Daniel I. Chasman, Braxton D. Mitchell, Jane Maguire, Jaakko Kaprio, Martin Farrall, Olli T. Raitakari, Tobias Kurth, M. Arfan Ikram, Alex P. Reiner, W. T. Longstreth, Peter M. Rothwell, David P. Strachan, Pankaj Sharma, Sudha Seshadri, Lydia Quaye, Lynn Cherkas, Markus Schürks, Jonathan Rosand, Lannie Ligthart, Giorgio B. Boncoraglio, George Davey Smith, Cornelia M. van Duijn, Bradford B. Worrall, Dale R. Nyholt, Hugh S. Markus, Arn M. J. M. van den Maagdenberg, Chris Cotsapas, John‐Anker Zwart, Aarno Palotie, Martin Dichgans, Unnur Þorsteinsdóttir, Anita L. DeStefano, Christopher Levi, Sólveig Grétarsdóttir, Peter Donnelly, Inês Barroso, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Christopher G. Mathew, Robert Plomin, Anna Rautanen, S. J. Sawcer, Richard C Trembath F, Ananth C. Viswanathan, Nicholas Wood, Chris C. A. Spencer, Gavin Band, Celine Bellengues, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard D. Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Sarah Hunt, Sarah Edkind, Rhian Gwilliam, Suzannah J. Bumpstead, Serge Dronv, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T McCann, Jennifer Liddle, Simon Potter, Rathi Ravindrarajah, Michelle Rickette, Matthew Waller, Paul A. Weston, Sara Widaa, Pamela Whittaker, Padhraig Gormley, Francesco Bettella, George McMahon, Unda Todt, Priit Palta, Eija Hämäläinen, Stacy Steinberg, Hreinn Stefánsson, Ville Artto, Mari Kaunisto, Jean Schoenen, Rune R. Frants, Guntram Borck, Hartmut Göbel, Axel Heinze, Katja Heinze‐Kuhn, Bertram Müller-Myhsok

Bibliographic record

VenueNeurology · 2015
Typereview
Languageen
FieldMedicine
TopicMigraine and Headache Studies
Canadian institutionsnot available
FundersFP7 HealthOffice of Research on Women's HealthNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Cancer InstituteNational Institute on Drug AbuseGGZ inGeestNational Institute on AgingNational Institute on Alcohol Abuse and AlcoholismMassachusetts General HospitalScottish Funding CouncilNIHR Cambridge Biomedical Research CentreYale UniversityUniversity of Texas Health Science Center at HoustonTurun YliopistoUniversitätsklinikum Hamburg-EppendorfNational Institute of Allergy and Infectious DiseasesAustralian Research CouncilEuropean Social FundMedical Research CouncilUniversiteit LeidenNational Heart, Lung, and Blood InstituteStanley Center for Psychiatric Research, Broad InstituteUniversitätsklinikum TübingenNational Institutes of HealthHeinz Nixdorf StiftungNIHR Oxford Biomedical Research CentreVincent Fairfax Family FoundationCentre for Medical Systems BiologyUniversität UlmPaavo Nurmen SäätiöTampereen TuberkuloosisäätiöUniversité de BordeauxNational Institute of Child Health and Human DevelopmentEmil Aaltosen SäätiöLudwig-Maximilians-Universität MünchenOffice of Research and DevelopmentUniversitair Medisch Centrum GroningenNational Institute for Health and Care ResearchCenters for Disease Control and PreventionLeids Universitair Medisch CentrumNederlandse Organisatie voor Wetenschappelijk OnderzoekTampereen YliopistoJuho Vainion SäätiöZonMwU.S. Public Health ServiceStiftung zur Erforschung der Vaskulären DemenzTrimbos-instituutGGZ DrentheGGZ FrieslandDeutsche ForschungsgemeinschaftMünchner Zentrum für GesundheitswissenschaftenUniversity of WashingtonRivierduinenInstitut National de la Santé et de la Recherche MédicaleSamfundet FolkhälsanMinistero della SaluteBritish Heart FoundationNational Center for Advancing Translational SciencesEuropean Science FoundationBundesministerium für Bildung und ForschungTerveyden ja hyvinvoinnin laitosImperial College LondonKing's College LondonAcademy of FinlandNational Institute of Mental HealthHelse Sør-Øst RHFHunter Medical Research InstituteUniversity of BristolKelaErasmus Medisch CentrumVrije Universiteit AmsterdamUniversity of OxfordNational Health and Medical Research CouncilTurun Yliopistollinen KeskussairaalaAmerican Heart AssociationSuomen KulttuurirahastoUK-India Education and Research InitiativeStroke AssociationUniversitetet i OsloWellcome TrustJohns Hopkins UniversityNational Eye InstituteHelsingin YliopistoFolkhälsanin TutkimussäätiöInstitute of GeneticsBroad InstituteQIMR Berghofer Medical Research InstituteNational Human Genome Research InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesHelsingin ja Uudenmaan SairaanhoitopiiriCambridge Institute for Medical Research, University of CambridgeChronic Disease Research FoundationNorges Teknisk-Naturvitenskapelige UniversitetBiomedicum Helsinki-säätiöHartstichtingCedars-Sinai Medical CenterEuropean CommissionSchool of Medicine, Boston UniversityNederlands Instituut voor Onderzoek van de GezondheidszorgU.S. Department of Veterans AffairsAmgenNIH Clinical CenterJuvenile Diabetes Research Foundation International
KeywordsMigraineAuraMigraine with auraStroke (engine)Familial hemiplegic migraineGenome-wide association studyIschemic strokeGenetic variationMedicineGenetic correlationGeneticsBiologyBioinformaticsInternal medicineSingle-nucleotide polymorphismGeneIschemiaGenotype

Abstract

fetched live from OpenAlex

OBJECTIVE: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. METHODS: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. RESULTS: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10(-20) for the CE score in MO). CONCLUSIONS: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

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)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.087
GPT teacher head0.361
Teacher spread0.274 · 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 designNot applicable
Domainnot available
GenreReview

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".

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Citations115
Published2015
Admission routes1
Has abstractyes

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