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

William J Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R Harper, Julia Ramirez, Sophie Garnier, Stefan van Duijvenboden, Antoine R Baldassari, Maria Pina Concas, ThuyVy Duong, Luisa Foco, Jonas L Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L SantolallaColleen M Sitlani, Negin Soroush, Sébastien Thériault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-François Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Rebecca D Jackson, Jan A Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W Macfarlane, Alanna C Morrison, Pau Navarro, David J Porteous, Peter Paul Pramstaller, Alexander P Reiner, Larisa G. Tereshchenko*, Patricia B Munroe*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

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.

OriginalsprogEngelsk
Sider (fra-til)1411
TidsskriftNature communications
Vol/bind14
Udgave nummer1
DOI
StatusUdgivet - 14 mar. 2023

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© 2023. The Author(s).

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