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Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Young, William J; Haessler, Jeffrey; Benjamins, Jan-Walter; Repetto, Linda; Yao, Jie; Isaacs, Aaron; Harper, Andrew R; ... Munroe, Patricia B; + view all (2023) Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease. Nature Communications , 14 (1) , Article 1411. 10.1038/s41467-023-36997-w. Green open access

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Abstract

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.

Type: Article
Title: Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-023-36997-w
Publisher version: https://doi.org/10.1038/s41467-023-36997-w
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Humans, Cardiovascular Diseases, Atrioventricular Block, Genome-Wide Association Study, Risk Factors, Arrhythmias, Cardiac, Electrocardiography, Biomarkers
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
URI: https://discovery.ucl.ac.uk/id/eprint/10167075
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