Evidence map›Paper›PMID 25691686›Full record

Trial reportCirculation. Cardiovascular genetics2015

Common and rare variants in SCN10A modulate the risk of atrial fibrillation.

Javad Jabbari, Morten S Olesen, Lei Yuan, Jonas B Nielsen, Bo Liang, Vincenzo Macri, Ingrid E Christophersen, Nikolaj Nielsen, Ahmad Sajadieh, Patrick T Ellinor and 5 more

Erratum issuedOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 70 citations in OpenAlex.

  1. Trial
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  3. MOG1medRxiv : the preprint server for health sciences · 2025
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  5. Heterologous expression of the human wild-type and variant NaNeurogastroenterology and motility · 2024
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  6. Review
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  8. Patient-specific induced pluripotent stem cell properties implicate CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  9. Molecular and Functional Relevance of NaInternational journal of molecular sciences · 2023
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Atrial fibrillation-a complex polygenetic disease.European journal of human genetics : EJHG · 2021
    Review
  15. Genetic insight into sick sinus syndrome.European heart journal · 2021
    Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Inhibition of NaBasic research in cardiology · 2020
    Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

15 authors at 2 institutions in 3 countries.

Javad JabbariFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Morten S OlesenFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Lei YuanFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Jonas B NielsenFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Bo LiangFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Vincenzo MacriFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Ingrid E ChristophersenFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Nikolaj NielsenFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Ahmad SajadiehFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Patrick T EllinorFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Morten GrunnetFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Stig HaunsøFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Anders G HolstFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Jesper H SvendsenFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.).
Thomas JespersenFrom the The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Department of Biomedical Sciences (J.J., M.S.O., L.Y., J.B.N., B.L., N.N., M.G., S.H., A.G.H., J.H.S., T.J.), Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet (J.J., M.S.O., J.B.N., S.H., A.G.H., J.H.S.), and Department of Clinical Medicine (S.H., J.H.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA (M.V., P.T.E) and Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E); Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Rud, Norway (I.E.C.); Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Bispebjerg, Denmark (A.S.); and LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark (S.H.). thojes@sund.ku.dk.
Broad Institute · USJisc · GB

Funding

IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
Determining the Role of the Potassium Channel, KCNN3, in Atrial FibrillationR01HL104156 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2010 to 2013
$2.1M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
The Genetic Basis of Atrial FibrillationK23HL071632 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2003 to 2007
$785k
NHLBI NIH HHS K23 HL071632NHLBI NIH HHS K24 HL105780NHLBI NIH HHS K24HL105780NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01HL092577NHLBI NIH HHS R01 HL104156NHLBI NIH HHS R01HL104156
6 · The paper itself

Abstract

backgroundGenome-wide association studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A, encoding the voltage-gated Nav1.8 sodium channel, is associated with PR-interval prolongation and atrial fibrillation (AF). Single nucleotide polymorphism rs6800541 is in high linkage disequilibrium with the nonsynonymous variant in SCN10A, rs6795970 (V1073A, r(2)=0.933). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF. METHODS AND

resultsSCN10A was sequenced in 225 AF patients in whom there was no evidence of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants was performed by whole-cell patch-clamping. In the lone AF cohort, 9 rare missense variants and 1 splice site donor variant were detected. Interestingly, AF patients were found to have higher G allele frequency of rs6795970, which encodes the alanine variant at position 1073 (described from here on as A1073, odds ratio =1.35 [1.16-1.54]; P=2.3×10(-5)). Both of the common variants, A1073 and P1092, induced a gain-of-channel function, whereas the rare missense variants, V94G and R1588Q, resulted in a loss-of-channel function.

conclusionsThe common variant A1073 is associated with increased susceptibility to AF. Both rare and common variants have effect on the function of the channel, indicating that these variants influence susceptibility to AF. Hence, our study suggests that SCN10A variations are involved in the genesis of AF.

Indexed as

Atrial FibrillationGenetic Predisposition to DiseaseGenome-Wide Association StudyLinkage DisequilibriumNAV1.8 Voltage-Gated Sodium ChannelPolymorphism, Single NucleotideAdolescentAdultAge of OnsetHumansMaleMiddle AgedNAV1.8 Voltage-Gated Sodium ChannelSCN10A protein, humanatrial fibrillation arrhythmiaelectrophysiologygenetic polymorphismgenome-wide association studygenotypingSCN10Avoltage-gated sodium channel alpha subunit Nav1.8

Identifiers

PMID25691686
PMCPMC4392342
OpenAlexW1967775917

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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.