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Verweij N, Benjamins JW, Morley MP, et al. The Genetic Makeup of the Electrocardiogram. Cell Syst. 2020;11(3):229-238.e5doi: 10.1016/j.cels.2020.08.005.
Verweij, N., Benjamins, J. W., Morley, M. P., van de Vegte, Y. J., Teumer, A., Trenkwalder, T., Reinhard, W., Cappola, T. P., & van der Harst, P. (2020). The Genetic Makeup of the Electrocardiogram. Cell systems, 11(3), 229-238.e5. https://doi.org/10.1016/j.cels.2020.08.005
Verweij, Niek, et al. "The Genetic Makeup of the Electrocardiogram." Cell systems vol. 11,3 (2020): 229-238.e5. doi: https://doi.org/10.1016/j.cels.2020.08.005
Verweij N, Benjamins JW, Morley MP, van de Vegte YJ, Teumer A, Trenkwalder T, Reinhard W, Cappola TP, van der Harst P. The Genetic Makeup of the Electrocardiogram. Cell Syst. 2020 Sep 23;11(3):229-238.e5. doi: 10.1016/j.cels.2020.08.005. Epub 2020 Sep 10. PMID: 32916098; PMCID: PMC7530085.
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Cell Syst. 2020 Sep 23;11(3):229-238.e5. doi: 10.1016/j.cels.2020.08.005. Epub 2020 Sep 10.

The Genetic Makeup of the Electrocardiogram.

Cell systems

Niek Verweij, Jan-Walter Benjamins, Michael P Morley, Yordi J van de Vegte, Alexander Teumer, Teresa Trenkwalder, Wibke Reinhard, Thomas P Cappola, Pim van der Harst

Affiliations

  1. University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands; Genomics plc, Oxford, UK. Electronic address: [email protected].
  2. University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
  3. Cardiovascular Institute, Perelman School of Medicine , University of Pennsylvania, Philadelphia, USA.
  4. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  5. Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technical University Munich, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
  6. Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technical University Munich, Munich, Germany.
  7. Division of Cardiovascular Medicine at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.
  8. University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands; Department of Cardiology, Heart and Lung Division, University Medical Center Utrecht, Utrecht, the Netherlands.

PMID: 32916098 PMCID: PMC7530085 DOI: 10.1016/j.cels.2020.08.005

Abstract

The electrocardiogram (ECG) is one of the most useful non-invasive diagnostic tests for a wide array of cardiac disorders. Traditional approaches to analyzing ECGs focus on individual segments. Here, we performed comprehensive deep phenotyping of 77,190 ECGs in the UK Biobank across the complete cycle of cardiac conduction, resulting in 500 spatial-temporal datapoints, across 10 million genetic variants. In addition to characterizing polygenic risk scores for the traditional ECG segments, we identified over 300 genetic loci that are statistically associated with the high-dimensional representation of the ECG. We established the genetic ECG signature for dilated cardiomyopathy, associated the BAG3, HSPB7/CLCNKA, PRKCA, TMEM43, and OBSCN loci with disease risk and confirmed this association in an independent cohort. In total, our work demonstrates that a high-dimensional analysis of the entire ECG provides unique opportunities for studying cardiac biology and disease and furthering drug development. A record of this paper's transparent peer review process is included in the Supplemental Information.

Copyright © 2020 Elsevier Inc. All rights reserved.

Keywords: cardiac conduction; cardiovascular risk; complex disease; dilated cardiomyopathy; electrocardiogram; electrophysiology; genetics; genome wide association

Conflict of interest statement

Declaration of Interests N.V. is a paid consultant for Regeneron Pharmaceuticals. The other authors declare no competing interests.

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