MétaCan
Menu
Back to cohort
Record W2801007324 · doi:10.1161/circgen.117.002037

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

2018· review· en· W2801007324 on OpenAlex
Honghuang Lin, Jessica van Setten, Albert V. Smith, Nathan A. Bihlmeyer, Helen R. Warren, Jennifer A. Brody, Farid Radmanesh, Leanne M. Hall, Niels Grarup, Martina Müller‐Nurasyid, Thibaud Boutin, Niek Verweij, Henry J. Lin, Ruifang Li‐Gao, Marten E. van den Berg, Jonathan Marten, Stefan Weiß, Bram P. Prins, Jeffrey Haessler, Leo‐Pekka Lyytikäinen, Hao Mei, Tamara B. Harris, Lenore J. Launer, Man Li, Álvaro Alonso, Elsayed Z. Soliman, John Connell, Paul L. Huang, Lu‐Chen Weng, Heather Jameson, William J. Hucker, Alan Hanley, Nathan R. Tucker, Yii-Der Ida Chen, Joshua C. Bis, Kenneth Rice, Colleen M. Sitlani, Jan A. Kors, Zhijun Xie, Chengping Wen, Jared W. Magnani, Christopher P. Nelson, Jørgen K. Kanters, Moritz F. Sinner, Konstantin Strauch, Annette Peters, Mélanie Waldenberger, Thomas Meitinger, Jette Bork‐Jensen, Oluf Pedersen, Allan Linneberg, Igor Rudan, Rudolf A. de Boer, Peter van der Meer, Jie Yao, Xiuqing Guo, Kent D. Taylor, Nona Sotoodehnia, Jerome I. Rotter, Dennis O. Mook‐Kanamori, Stella Trompet, Fernando Rivadeneira, André G. Uitterlinden, Mark Eijgelsheim, Sandosh Padmanabhan, Blair H. Smith, Henry Völzke, Stephan B. Felix, Georg Homuth, Uwe Völker, Massimo Mangino, Timothy D. Spector, Michiel L. Bots, Marco Perez, Mika Kähönen, Olli T. Raitakari, Vilmundur Guðnason, Dan E. Arking, Patricia B. Munroe, Bruce M. Psaty, Cornelia M. van Duijn, Emelia J. Benjamin, Jonathan Rosand, Nilesh J. Samani, Torben Hansen, Stefan Kääb, Ozren Polašek, Pim van der Harst, Susan R. Heckbert, J. Wouter Jukema, Bruno H. Stricker, Caroline Hayward, Marcus Dörr, Yalda Jamshidi, Folkert W. Asselbergs, Charles Kooperberg, Terho Lehtimäki, James Wilson, Patrick T. Ellinor, Steven A. Lubitz, Aaron Isaacs

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.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueCirculation Genomic and Precision Medicine · 2018
Typereview
Languageen
FieldMedicine
TopicCardiac electrophysiology and arrhythmias
Canadian institutionsnot available
FundersInstitute of GeneticsNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesNational Heart, Lung, and Blood InstituteCARIM School for Cardiovascular Diseases, Universiteit MaastrichtWake Forest School of MedicineNational Institutes of HealthSchool of Medicine, Stanford UniversityHjartaverndTurun Yliopistollinen KeskussairaalaNovo Nordisk Foundation Center for Basic Metabolic ResearchTaysTurun YliopistoHáskóli ÍslandsUniversitair Medisch Centrum GroningenNational Center for Advancing Translational SciencesMedical Research CouncilLeids Universitair Medisch CentrumTechnische Universität MünchenTampereen YliopistoUniversiteit LeidenUniversity of GlasgowKing's College LondonFaculty of Health and Medical Sciences, University of Western AustraliaRijksuniversiteit GroningenUniversity of LeicesterUniversity of DundeeKaiser Permanente Washington Health Research InstituteNetherlands Heart InstituteDeutsches Zentrum für Herz-KreislaufforschungBroad InstituteBritish Heart FoundationUniversity of PittsburghUniversiteit MaastrichtRigshospitaletUniversity of WashingtonJohns Hopkins UniversitySchool of Medicine, Boston UniversityUniversity College LondonEmory UniversityKaiser PermanenteLudwig-Maximilians-Universität MünchenNational Institute for Health and Care ResearchQueen Mary University of LondonRegion HovedstadenNovo NordiskMassachusetts General Hospital
KeywordsVariation (astronomy)Coding (social sciences)Interval (graph theory)Genetic variationStatisticsMathematicsBiologyGeneticsCombinatoricsPhysics

Abstract

fetched live from OpenAlex

Background: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability. Methods: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval. Results: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction ( P <1.2×10 −6 ), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 ( P =5.9×10 −11 ) and SCN5A ( P =1.1×10 −7 ) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus. Conclusions: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health.

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)0.001
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: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.995
Threshold uncertainty score0.895

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 integrity0.0000.001
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 head0.054
GPT teacher head0.332
Teacher spread0.278 · 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