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Sequence variants with large effects on cardiac electrophysiology and disease

Author

Listed:
  • Kristjan Norland

    (deCODE genetics/Amgen Inc.)

  • Gardar Sveinbjornsson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Rosa B. Thorolfsdottir

    (deCODE genetics/Amgen Inc.)

  • Olafur B. Davidsson

    (deCODE genetics/Amgen Inc.)

  • Vinicius Tragante

    (deCODE genetics/Amgen Inc.
    Utrecht University)

  • Sridharan Rajamani

    (deCODE genetics/Amgen Inc.)

  • Anna Helgadottir

    (deCODE genetics/Amgen Inc.)

  • Solveig Gretarsdottir

    (deCODE genetics/Amgen Inc.)

  • Jessica Setten

    (Utrecht University)

  • Folkert W. Asselbergs

    (Utrecht University
    University College London
    University College London)

  • Jon Th. Sverrisson

    (Akureyri Hospital)

  • Sigurdur S. Stephensen

    (Landspitali-The National University Hospital of Iceland)

  • Gylfi Oskarsson

    (Landspitali-The National University Hospital of Iceland)

  • Emil L. Sigurdsson

    (University of Iceland
    Primary Health Care of the Capital Area)

  • Karl Andersen

    (Landspitali-The National University Hospital of Iceland
    University of Iceland)

  • Ragnar Danielsen

    (Landspitali-The National University Hospital of Iceland)

  • Gudmundur Thorgeirsson

    (deCODE genetics/Amgen Inc.
    Landspitali-The National University Hospital of Iceland
    University of Iceland)

  • Unnur Thorsteinsdottir

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • David O. Arnar

    (deCODE genetics/Amgen Inc.
    Landspitali-The National University Hospital of Iceland
    University of Iceland)

  • Patrick Sulem

    (deCODE genetics/Amgen Inc.)

  • Hilma Holm

    (deCODE genetics/Amgen Inc.)

  • Daniel F. Gudbjartsson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Kari Stefansson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

Abstract

Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.

Suggested Citation

  • Kristjan Norland & Gardar Sveinbjornsson & Rosa B. Thorolfsdottir & Olafur B. Davidsson & Vinicius Tragante & Sridharan Rajamani & Anna Helgadottir & Solveig Gretarsdottir & Jessica Setten & Folkert W, 2019. "Sequence variants with large effects on cardiac electrophysiology and disease," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12682-9
    DOI: 10.1038/s41467-019-12682-9
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