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Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation

2023· review· en· 89 citations· W4378715403 on OpenAlex· 10.1038/s41588-023-01410-1

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.
Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

Full frame distilled prediction

Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

Candidate categories
Meta-epidemiology (narrow), Research integrity
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Meta-analysisConsensus signal: Meta-analysis
Genre
Candidate signal: ReviewConsensus signal: Review
Teacher disagreement score
0.222
Threshold uncertainty score
1.000
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0040.001
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

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

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.

Opus teacher head0.035
GPT teacher head0.330
Teacher spread
0.295 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

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.

The record

Venue
Nature Genetics
Topic
Cardiovascular Issues in Pregnancy
Field
Medicine
Canadian institutions
Vancouver General HospitalUniversity of British Columbia
Funders
Common FundNational Institute of Diabetes and Digestive and Kidney DiseasesNational Cancer InstituteNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteEuropean Regional Development FundAstraZenecaNational Health and Medical Research CouncilNational Institutes of HealthU.S. Department of DefenseSociété Française de CardiologieMedical Research CouncilNSW Ministry of HealthFédération Française de CardiologieAgence Nationale de la RechercheNational Institute of General Medical SciencesCenter for Individualized Medicine, Mayo ClinicBritish Heart FoundationNational Institute for Health and Care ResearchNIH Office of the DirectorCardiac Society of Australia and New ZealandMichael Smith Health Research BCInstituto de Salud Carlos IIICentre Hospitalier Universitaire de Clermont-FerrandFONDATION ALZHEIMERA. Alfred Taubman Medical Research InstituteVictor Chang Cardiac Research InstituteUniversity of MichiganCanadian Institutes of Health ResearchAmerican Heart AssociationHeart and Stroke Foundation of Canada
Keywords
ScadBiologyCoronary artery diseaseGenome-wide association studyMyocardial infarctionGenetic associationBioinformaticsGeneGeneticsInternal medicineSingle-nucleotide polymorphismMedicineGenotype
Has abstract in OpenAlex
yes