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Nat Commun. 2019 Oct 22;10(1):4803. doi: 10.1038/s41467-019-12682-9.

Sequence variants with large effects on cardiac electrophysiology and disease.

Author information

1
deCODE genetics/Amgen Inc., Reykjavik, Iceland.
2
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
3
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
4
Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.
5
Health Data Research UK and Institute of Health Informatics, University College London, London, UK.
6
Department of Internal Medicine, Akureyri Hospital, Eyrarlandsvegur, 600, Akureyri, Iceland.
7
Department of Paediatric Cardiology, Children's Hospital, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
8
Department of Family Medicine, University of Iceland, Reykjavik, Iceland.
9
Department of Development, Primary Health Care of the Capital Area, Reykjavik, Iceland.
10
Division of Cardiology, Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
11
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
12
deCODE genetics/Amgen Inc., Reykjavik, Iceland. Daniel.Gudbjartsson@decode.is.
13
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland. Daniel.Gudbjartsson@decode.is.
14
deCODE genetics/Amgen Inc., Reykjavik, Iceland. kstefans@decode.is.
15
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. kstefans@decode.is.

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.

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