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Record W2121187319 · doi:10.1161/strokeaha.113.002707

Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease

2013· review· en· W2121187319 on OpenAlex
Martin Dichgans, Rainer Malik, Inke R. König, Jonathan Rosand, Robert Clarke, Sólveig Grétarsdóttir, Guðmar Þorleifsson, Braxton D. Mitchell, Themistocles L. Assimes, Christopher Levi, Christopher J O Donnell, Myriam Fornage, Unnur Þorsteinsdóttir, Bruce M. Psaty, Christian Hengstenberg, Sudha Seshadri, Jeanette Erdmann, Joshua C. Bis, Annette Peters, Giorgio B. Boncoraglio, Winfried März, James F. Meschia, Sekar Kathiresan, M. Arfan Ikram, Ruth McPherson, Kāri Stefánsson, Cathie Sudlow, Muredach P. Reilly, J. Thompson, Pankaj Sharma, Jemma C. Hopewell, John C. Chambers, Hugh Watkins, Peter M. Rothwell, Robert J. Roberts, Hugh S. Markus, Nilesh J. Samani, Martin Farrall, Heribert Schunkert, Andreas Gschwendtner, Steve Bevan, Yu‐Ching Chen, Anita L. DeStefano, Eugenio Parati, Andreas Ziegler, Eric Boerwinkle, Hilma Hólm, Marcus Fischer, Thorsten Kessler, Christina Willenborg, Reijo Laaksonen, Benjamin F. Voight, Alexandre F.R. Stewart, Daniel J. Rader, Alistair S. Hall, Jaspal S. Kooner

Why this work is in the frame

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

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueStroke · 2013
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsCanadian Heart Research CentreUniversity of Ottawa
FundersInstitute of GeneticsNational Center for Advancing Translational SciencesNational Center for Research ResourcesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institute for Health and Care ResearchNational Institute on AgingU.S. Public Health ServiceNational Institutes of HealthTechnische Universität MünchenSchool of Medicine, Stanford UniversityUniversität zu LübeckInstitute for Translational Medicine and TherapeuticsCanadian Institutes of Health ResearchUniversity of OttawaUniversity of Texas Health Science Center at HoustonDeutsches Zentrum für Herz-KreislaufforschungImperial College LondonBroad InstituteNational Institute of Neurological Disorders and StrokeBritish Heart FoundationUniversity of PennsylvaniaNational Human Genome Research InstituteTaysNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustUniversity of LeedsSchool of Medicine, Boston University
KeywordsGenome-wide association studyCoronary artery diseaseMedicineHeritabilityGenetic associationGeneticsInternal medicineDiseaseStroke (engine)Clinical significanceCardiologyBioinformaticsSingle-nucleotide polymorphismBiologyGenotypeGene

Abstract

fetched live from OpenAlex

BACKGROUND AND PURPOSE: Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. METHODS: Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype. RESULTS: Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4)). CONCLUSIONS: Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.881
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

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

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 head0.027
GPT teacher head0.299
Teacher spread0.273 · 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