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The genetic makeup of the electrocardiogram

View ORCID ProfileNiek Verweij, Jan-Walter Benjamins, Michael P. Morley, View ORCID ProfileYordi van de Vegte, View ORCID ProfileAlexander Teumer, View ORCID ProfileTeresa Trenkwalder, View ORCID ProfileWibke Reinhard, View ORCID ProfileThomas P. Cappola, View ORCID ProfilePim van der Harst
doi: https://doi.org/10.1101/648527
Niek Verweij
aUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands
bGenomics plc, Oxford, United Kingdom
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  • For correspondence: p.van.der.harst@umcg.nl n.verweij@umcg.nl
Jan-Walter Benjamins
aUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands
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Michael P. Morley
cThe Cardiovascular Institute at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
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Yordi van de Vegte
aUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands
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Alexander Teumer
dInstitute for Community Medicine, University Medicine Greifswald, Germany
eDZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
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Teresa Trenkwalder
fKlinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technical University Munich, Munich, Germany
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Wibke Reinhard
fKlinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technical University Munich, Munich, Germany
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Thomas P. Cappola
gDivision of Cardiovascular Medicine at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
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Pim van der Harst
aUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands
hUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands
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  • For correspondence: p.van.der.harst@umcg.nl n.verweij@umcg.nl
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Abstract

Since its original description in 1893 by Willem van Einthoven, the electrocardiogram (ECG) has been instrumental in the recognition of a wide array of cardiac disorders1,2. Although many electrocardiographic patterns have been well described, the underlying biology is incompletely understood. Genetic associations of particular features of the ECG have been identified by genome wide studies. This snapshot approach only provides fragmented information of the underlying genetic makeup of the ECG. Here, we follow the effecs of individual genetic variants through the complete cardiac cycle the ECG represents. We found that genetic variants have unique morphological signatures not identfied by previous analyses. By exploiting identified abberations of these morphological signatures, we show that novel genetic loci can be identified for cardiac disorders. Our results demonstrate how an integrated approach to analyse high-dimensional data can further our understanding of the ECG, adding to the earlier undertaken snapshot analyses of individual ECG components. We anticipate that our comprehensive resource will fuel in silico explorations of the biological mechanisms underlying cardiac traits and disorders represented on the ECG. For example, known disease causing variants can be used to identify novel morphological ECG signatures, which in turn can be utilized to prioritize genetic variants or genes for functional validation. Furthermore, the ECG plays a major role in the development of drugs, a genetic assessment of the entire ECG can drive such developments.

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  • http://www.ecgenetics.org

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted May 24, 2019.
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The genetic makeup of the electrocardiogram
Niek Verweij, Jan-Walter Benjamins, Michael P. Morley, Yordi van de Vegte, Alexander Teumer, Teresa Trenkwalder, Wibke Reinhard, Thomas P. Cappola, Pim van der Harst
bioRxiv 648527; doi: https://doi.org/10.1101/648527
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The genetic makeup of the electrocardiogram
Niek Verweij, Jan-Walter Benjamins, Michael P. Morley, Yordi van de Vegte, Alexander Teumer, Teresa Trenkwalder, Wibke Reinhard, Thomas P. Cappola, Pim van der Harst
bioRxiv 648527; doi: https://doi.org/10.1101/648527

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