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Record W2221162814 · doi:10.1212/nxg.0000000000000010

Genetic analysis for a shared biological basis between migraine and coronary artery disease

2015· article· en· W2221162814 on OpenAlexfundno aff
Bendik S. Winsvold, Christopher P. Nelson, Rainer Malik, Padhraig Gormley, Verneri Anttila, Jason Vander Heiden, Katherine S. Elliott, L.M. Jacobsen, Priit Palta, Najaf Amin, Boukje de Vries, Eija Hämäläinen, Tobias Freilinger, M. Arfan Ikram, Thorsten Kessler, Markku Koiranen, Lannie Ligthart, George McMahon, Linda M. Pedersen, Christina Willenborg, Hong‐Hee Won, Jes Olesen, Ville Artto, Themistocles L. Assimes, Stefan Blankenberg, Dorret I. Boomsma, Lynn Cherkas, George Davey Smith, Stephen E. Epstein, Jeanette Erdmann, Michel D. Ferrari, Hartmut Göbel, Alistair S. Hall, Marjo‐Riitta Järvelin, Mikko Kallela, Jaakko Kaprio, Sekar Kathiresan, Terho Lehtimäki, Ruth McPherson, Winfried März, Dale R. Nyholt, Christopher J. O’Donnell, Lydia Quaye, Daniel J. Rader, Olli T. Raitakari, Robert J. Roberts, Heribert Schunkert, Markus Schürks, Alexandre F.R. Stewart, Gisela M. Terwindt, Unnur Þorsteinsdóttir, Arn M. J. M. van den Maagdenberg, Cornelia M. van Duijn, Maija Wessman, Tobias Kurth, Christian Kubisch, Martin Dichgans, Daniel I. Chasman, Chris Cotsapas, John‐Anker Zwart, Nilesh J. Samani, Aarno Palotie, Leonore J. Launer, Alfons Macaya, Patricia Pozo‐Rosich, Bru Cormand, Jessica Fernandez, Marta Vila‐Pueyo, Cèlia Sintas, Anne Francke Christensen, Ann-Louise Esserlind, Tõnu Esko, E Garcia Cuenca, Bertram Müller‐Myhsok, Alice Pressman, Arn van den Maagdenberg, Rune R. Frants, Brenda W.J.H. Penninx, Andrea Carmine Belin, Nancy L. Pedersen, Markus Schuerks, Nick Eriksson, Devin Absher, Stephen P. Fortmann, Alan S. Go, Mark A. Hlatky, Carlos Iribarren, Joshua Knowles, Richard H. Myers, Thomas Quertermous, Steven Sidney, Neil Risch, Hua Tang, Tanja Zeller, Arne Schillert, Philipp S. Wild, Andreas Ziegler, Renate B. Schnabel, Christoph Sinning, Karl J. Lackner, Laurence Tiret, Viviane Nicaud, François Cambien, Christoph Bickel, Hans J. Rupprecht, Claire Perret, Carole Proust, Thomas Münzel, Maja Barbalić, Joshua C. Bis, Eric Boerwinkle, Ida Yii-Der Chen, L. Adrienne Cupples, Abbas Dehghan, Serkalem Demissie-Banjaw, Aaron R. Folsom, Nicole L. Glazer, Vilmundur Guðnason, Tamara Harris, Susan R. Heckbert, Daniel Levy, Thomas Lumley, Kristin D. Marciante, Alanna C. Morrison, Bruce M. Psaty, Kenneth Rice, Jerome I. Rotter, David S. Siscovick, Nicholas L. Smith, Albert V. Smith, Kent D. Taylor, Kelly A. Volcik, Jaqueline Whitteman, Ramachandran S. Vasan, Albert Hofman, André G. Uitterlinden, Sólveig Grétarsdóttir, Jeffrey R. Gulcher, Hilma Hólm, Augustine Kong, Guðmundur Þorgeirsson, Karl Andersen, Guðmar Þorleifsson, Marcus Fischer, Anika Großhennig, Christian Hengstenberg, Inke R. König, Wolfgang Lieb, Patrick Linsel‐Nitschke, Michael Preuß, Klaus Stark, Stefan Schreiber, H.-Erich Wichmann, Zouhair Aherrahrou, Petra Bruse, Angela Doering, Thomas Illig, Norman Klopp, Christina Loley, Anja Medack, Christina Meisinger, Thomas Meitinger, Janja Nahrstaedt, Annette Peters, Arnika Kathleen Wagner, Bernhard Böhm, Harald Dobnig, Tanja B. Grammer, Eran Halperin, Michael M. Hoffmann, Marcus E. Kleber, Reijo Laaksonen, Andreas Meinitzer, Bernhard R. Winkelmann, Stefan Pilz, Wilfried Renner, Hubert Scharnagl, Tatjana Stojaković, Andreas Tomaschitz, Karl Winkler, Benjamin F. Voight, Candace Guiducci, Noël P. Burtt, Stacey B. Gabriel, Roberto Elosúa, Leena Peltonen, Veikko Salomaa, Stephen M. Schwartz, Olle Melander, David Altshuler, Li Chen, Sonny Dandona, George A. Wells, Olga Jarinova, Muredach P. Reilly, Mingyao Li, Liming Qu, Robert Wilensky, William Matthai, Håkon Håkonarson, Joe Devaney, Mary Susan Burnett, Augusto D. Pichard, Kenneth M. Kent, Lowell F. Satler, Joseph Lindsay, Ron Waksman, Christopher W. Knouff, Dawn Waterworth, Max Walker, Vincent Mooser, J. R. Thompson, Peter S. Braund, Benjamin J. Wright, Anthony J. Balmforth, Stephen G. Ball

Bibliographic record

VenueNeurology Genetics · 2015
Typearticle
Languageen
FieldMedicine
TopicMigraine and Headache Studies
Canadian institutionsnot available
FundersInstitute of GeneticsNational Institute of Neurological Disorders and StrokeNational Cancer InstituteNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute on Alcohol Abuse and AlcoholismUniversitätsmedizin der Johannes Gutenberg-Universität MainzUniversitätsklinikum Hamburg-EppendorfNational Institutes of HealthKing's College LondonAcademy of FinlandTerveyden ja hyvinvoinnin laitosHelsingin ja Uudenmaan SairaanhoitopiiriTurun Yliopistollinen KeskussairaalaCentre for Medical Systems BiologyUniversité de BordeauxSuomen KulttuurirahastoOulun YliopistoTurun YliopistoUniversity of PennsylvaniaMedizinische Universität GrazEmil Aaltosen SäätiöDeutsche ForschungsgemeinschaftNederlandse Organisatie voor Wetenschappelijk OnderzoekTechnische Universität MünchenTampereen YliopistoJuho Vainion SäätiöAvera Institute for Human GeneticsHáskóli ÍslandsBundesministerium für Bildung und ForschungSamfundet FolkhälsanUniversität zu LübeckQueensland University of TechnologyEberhard Karls Universität TübingenUniversiteit LeidenSchool of Medicine, Stanford UniversityInstitut National de la Santé et de la Recherche MédicaleKarl-Franzens-Universität GrazUniversity of BristolUniversität HeidelbergVrije Universiteit AmsterdamUniversity of OttawaDeutsches Zentrum für Herz-KreislaufforschungFP7 HealthImperial College LondonBiocenter, University of OuluNational Institute for Health and Care ResearchFolkhälsanin TutkimussäätiöEuropean CommissionNorges Teknisk-Naturvitenskapelige UniversitetTampereen TuberkuloosisäätiöKelaUniversity of LeedsMedical Research CouncilInstitute for Translational Medicine and TherapeuticsWellcome TrustPaavo Nurmen SäätiöZonMwAmgen
KeywordsMigraineAuraGenome-wide association studyMigraine with auraCoronary artery diseaseGenetic associationGeneticsDiseaseBioinformaticsBiologyMedicineInternal medicineSingle-nucleotide polymorphismGeneGenotype

Abstract

fetched live from OpenAlex

OBJECTIVE: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). METHODS: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. RESULTS: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). CONCLUSIONS: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

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)0.003
metaresearch head score (Gemma)0.010
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 score0.003
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.010
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
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 head0.097
GPT teacher head0.314
Teacher spread0.217 · 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".

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Citations74
Published2015
Admission routes1
Has abstractyes

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Same venueNeurology GeneticsSame topicMigraine and Headache StudiesFrench-language works237,207