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Record W2618913536 · doi:10.1038/ncomms15481

Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve

2017· article· en· W2618913536 on OpenAlexaff
Bo Yang, Wei Zhou, Jiao Jiao, Jonas B. Nielsen, Michael R. Mathis, Mahyar Heydarpour, Guillaume Lettre, Lasse Folkersen, Siddharth K. Prakash, Claudia Schurmann, Lars G. Fritsche, G.A. Farnum, Maoxuan Lin, Mohammad Othman, Whitney Hornsby, Anisa Driscoll, Alexandra Levasseur, Marc A. Thomas, Linda Farhat, Marie‐Pierre Dubé, Eric M. Isselbacher, Anders Franco‐Cereceda, Dongchuan Guo, Erwin P. Böttinger, G. Michael Deeb, Anna M. Booher, Sachin Kheterpal, Y. Eugene Chen, Hyun Min Kang, Jacob O. Kitzman, Heather J. Cordell, Bernard Keavney, Judith A. Goodship, Santhi K. Ganesh, Gonçalo R. Abecasis, Kim A. Eagle, Alan P. Boyle, Ruth J. F. Loos, Per Eriksson, Jean‐Claude Tardif, Chad M. Brummett, Dianna M. Milewicz, Simon C. Body, Cristen J. Willer

Bibliographic record

VenueNature Communications · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersNational Center for Advancing Translational SciencesNational Cancer InstituteNIH Office of the DirectorNational Human Genome Research InstituteNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteWalter Reed National Military Medical CenterNational Institutes of HealthH. Lundbeck A/SUniversity of OxfordNational Institute of Neurological Disorders and StrokeBritish Heart FoundationSeconda Università degli Studi di NapoliBroad InstituteCommon FundUniversity of Texas Health Science Center at HoustonUniversität HamburgUniversity of MiamiIcahn School of Medicine at Mount SinaiVanderbilt UniversityUniversity of ChicagoUniversity of TasmaniaHarvard UniversityUniversity of MichiganHjerteforeningenFundació Institut de Recerca Hospital Universitari Vall d’HebronUniversité de GenèveFonden til Lægevidenskabens FremmeHebrew University of JerusalemFondation LeducqNational Institute on Drug AbuseUniversity of PennsylvaniaUniversità degli Studi di Napoli Federico IILundbeckfondenA.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene FormaalAndrea and Charles Bronfman PhilanthropiesThoracic Surgery Foundation for Research and Education
KeywordsGATA4Bicuspid aortic valveInduced pluripotent stem cellTranscription factorBiologyHeart developmentHeart valveInternal medicineGeneAortic valveGeneticsMedicineEmbryonic stem cell

Abstract

fetched live from OpenAlex

Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.

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 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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.934
Threshold uncertainty score0.462

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
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 head0.022
GPT teacher head0.338
Teacher spread0.316 · 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 teacher head, 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".

Quick stats

Citations128
Published2017
Admission routes1
Has abstractyes

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