Sequence variants with large effects on cardiac electrophysiology and disease

Kristjan Norland, Gardar Sveinbjornsson, Rosa B. Thorolfsdottir, Olafur B. Davidsson, Vinicius Tragante, Sridharan Rajamani, Anna Helgadottir, Solveig Gretarsdottir, Jessica Setten, Folkert W. Asselbergs, Jon Th. Sverrisson, Sigurdur S. Stephensen, Gylfi Oskarsson, Emil L. Sigurdsson, Karl Andersen, Ragnar Danielsen, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, David O. Arnar, Patrick Sulem, Hilma Holm, Daniel F. Gudbjartsson () and Kari Stefansson ()
Additional contact information
Kristjan Norland: deCODE genetics/Amgen Inc.
Gardar Sveinbjornsson: deCODE genetics/Amgen Inc.
Rosa B. Thorolfsdottir: deCODE genetics/Amgen Inc.
Olafur B. Davidsson: deCODE genetics/Amgen Inc.
Vinicius Tragante: deCODE genetics/Amgen Inc.
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
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
Karl Andersen: Landspitali-The National University Hospital of Iceland
Ragnar Danielsen: Landspitali-The National University Hospital of Iceland
Gudmundur Thorgeirsson: deCODE genetics/Amgen Inc.
Unnur Thorsteinsdottir: deCODE genetics/Amgen Inc.
David O. Arnar: deCODE genetics/Amgen Inc.
Patrick Sulem: deCODE genetics/Amgen Inc.
Hilma Holm: deCODE genetics/Amgen Inc.
Daniel F. Gudbjartsson: deCODE genetics/Amgen Inc.
Kari Stefansson: deCODE genetics/Amgen Inc.

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12682-9

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