Evidence map›Paper›PMID 31600170›Full record

SynthesisJCI insight2019

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.

Alexander Teumer, Teresa Trenkwalder, Thorsten Kessler, Yalda Jamshidi, Marten E van den Berg, Bernhard Kaess, Christopher P Nelson, Rachel Bastiaenen, Marzia De Bortoli, Alessandra Rossini and 42 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.International journal of molecular sciences · 2024
    Review
  4. Review
  5. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2022
    Article
  6. Article
  7. Review
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

52 authors at 16 institutions in 5 countries.

Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Teresa TrenkwalderKlinik für Herz-und Kreislauferkrankungen, Deutsches Herzzentrum München, School of Medicine, Technical University of Munich, Munich, Germany.
Thorsten KesslerKlinik für Herz-und Kreislauferkrankungen, Deutsches Herzzentrum München, School of Medicine, Technical University of Munich, Munich, Germany.
Yalda JamshidiGenetics Research Centre, Institute of Molecular and Clinical Sciences, Saint George's University of London, London, United Kingdom.
Marten E van den BergDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
Bernhard KaessMedizinische Klinik I, St. Josefs-Hospital, Wiesbaden, Germany.
Christopher P NelsonDepartment of Cardiovascular Sciences, BHF Cardiovascular Research Centre, Leicester, United Kingdom.
Rachel BastiaenenCardiology Clinical Academic Group, Institute of Molecular and Clinical Sciences, Saint George's, University of London, London, United Kingdom.
Marzia De BortoliEurac Research, Institute for Biomedicine, affiliated with the University of Lübeck, Bolzano, Italy.
Alessandra RossiniEurac Research, Institute for Biomedicine, affiliated with the University of Lübeck, Bolzano, Italy.
Isabel DeisenhoferKlinik für Herz-und Kreislauferkrankungen, Deutsches Herzzentrum München, School of Medicine, Technical University of Munich, Munich, Germany.
Klaus StarkDepartment of Genetic Epidemiology, University Regensburg, Regensburg, Germany.
Solmaz AssaDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Peter S BraundDepartment of Cardiovascular Sciences, BHF Cardiovascular Research Centre, Leicester, United Kingdom.
Claudia CabreraClinical Pharmacology, William Harvey Research Institute, and.
Anna F DominiczakInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Martin GögeleEurac Research, Institute for Biomedicine, affiliated with the University of Lübeck, Bolzano, Italy.
Leanne M HallDepartment of Cardiovascular Sciences, BHF Cardiovascular Research Centre, Leicester, United Kingdom.
M Arfan IkramDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
Maryam KavousiDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
Karl J LacknerInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany.
Lifelines Cohort Study
Christian MüllerUniversity Heart & Vascular Center Hamburg, Hamburg, Germany.
Thomas MünzelDZHK, partner site Rhine-Main, Mainz, Germany.
Matthias NauckGerman Center for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
Sandosh PadmanabhanInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Norbert PfeifferDepartment of Ophthalmology, University Medical Center of the Johannes Gutenberg, University Mainz, Mainz, Germany.
Tim D SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Andre G UitterlindenDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
Niek VerweijDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Uwe VölkerGerman Center for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
Helen R WarrenClinical Pharmacology, William Harvey Research Institute, and.
Mobeen ZafarDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Stephan B FelixGerman Center for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
Jan A KorsDepartment of Medical Informatics, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Patricia B MunroeClinical Pharmacology, William Harvey Research Institute, and.
Cristian PattaroEurac Research, Institute for Biomedicine, affiliated with the University of Lübeck, Bolzano, Italy.
Christian FuchsbergerEurac Research, Institute for Biomedicine, affiliated with the University of Lübeck, Bolzano, Italy.
Georg SchmidtInnere Medizin I, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Heribert SchunkertKlinik für Herz-und Kreislauferkrankungen, Deutsches Herzzentrum München, School of Medicine, Technical University of Munich, Munich, Germany.
Peter P PramstallerEurac Research, Institute for Biomedicine, affiliated with the University of Lübeck, Bolzano, Italy.
Philipp S WildDZHK, partner site Rhine-Main, Mainz, Germany.
Pim van der HarstDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Bruno H StrickerDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
Renate B SchnabelUniversity Heart & Vascular Center Hamburg, Hamburg, Germany.
Nilesh J SamaniDepartment of Cardiovascular Sciences, BHF Cardiovascular Research Centre, Leicester, United Kingdom.
Christian HengstenbergDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Marcus DörrGerman Center for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
Elijah R BehrCardiology Clinical Academic Group, Institute of Molecular and Clinical Sciences, Saint George's University of London, London, United Kingdom.
Wibke ReinhardKlinik für Herz-und Kreislauferkrankungen, Deutsches Herzzentrum München, School of Medicine, Technical University of Munich, Munich, Germany.
Erasmus MC · NLInstitute for Biomedicine · ITUniversity Medical Center Groningen · NLDeutsches Herzzentrum München · DEJohannes Gutenberg University Mainz · DENIHR Leicester Cardiovascular Biomedical Research Unit · GBUniversitätsmedizin Greifswald · DEGerman Centre for Cardiovascular Research · DEQueen Mary University of London · GBSt George's, University of London · GBUniversity of Glasgow · GBKing's College London · GBMedical University of Vienna · ATSt. Josefs Hospital · DETUM Klinikum · DEUniversity of Regensburg · DE

Funding

British Heart Foundation PG/02/128British Heart Foundation PG/06/094/21278British Heart Foundation PG/12/38/29615Department of HealthMedical Research Council G9521010DMedical Research Council MR/N003403/1Wellcome Trust
6 · The paper itself

Abstract

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments.

Indexed as

AllelesDeath, Sudden, CardiacElectrocardiographyFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHeart VentriclesHumansMalePolymorphism, Single NucleotideShal Potassium ChannelsTranscriptomeVentricular FibrillationWhite PeopleKCND3 protein, humanShal Potassium ChannelsArrhythmiasCardiologyGeneticsGenetic variationIon channels

Identifiers

PMID31600170
PMCPMC6962032
OpenAlexW2979485010

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.