Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease Journal Articles uri icon

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abstract

  • AbstractThe 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.

authors

  • Young, William J
  • Haessler, Jeffrey
  • Benjamins, Jan-Walter
  • Repetto, Linda
  • Yao, Jie
  • Isaacs, Aaron
  • Harper, Andrew R
  • Ramirez, Julia
  • Garnier, Sophie
  • van Duijvenboden, Stefan
  • Baldassari, Antoine R
  • Concas, Maria Pina
  • Duong, ThuyVy
  • Foco, Luisa
  • Isaksen, Jonas L
  • Mei, Hao
  • Noordam, Raymond
  • Nursyifa, Casia
  • Richmond, Anne
  • Santolalla, Meddly L
  • Sitlani, Colleen M
  • Soroush, Negin
  • Thériault, Sébastien
  • Trompet, Stella
  • Aeschbacher, Stefanie
  • Ahmadizar, Fariba
  • Alonso, Alvaro
  • Brody, Jennifer A
  • Campbell, Archie
  • Correa, Adolfo
  • Darbar, Dawood
  • De Luca, Antonio
  • Deleuze, Jean-François
  • Ellervik, Christina
  • Fuchsberger, Christian
  • Goel, Anuj
  • Grace, Christopher
  • Guo, Xiuqing
  • Hansen, Torben
  • Heckbert, Susan R
  • Jackson, Rebecca D
  • Kors, Jan A
  • Lima-Costa, Maria Fernanda
  • Linneberg, Allan
  • Macfarlane, Peter W
  • Morrison, Alanna C
  • Navarro, Pau
  • Porteous, David J
  • Pramstaller, Peter P
  • Reiner, Alexander P
  • Risch, Lorenz
  • Schotten, Ulrich
  • Shen, Xia
  • Sinagra, Gianfranco
  • Soliman, Elsayed Z
  • Stoll, Monika
  • Tarazona-Santos, Eduardo
  • Tinker, Andrew
  • Trajanoska, Katerina
  • Villard, Eric
  • Warren, Helen R
  • Whitsel, Eric A
  • Wiggins, Kerri L
  • Arking, Dan E
  • Avery, Christy L
  • Conen, David
  • Girotto, Giorgia
  • Grarup, Niels
  • Hayward, Caroline
  • Jukema, J Wouter
  • Mook-Kanamori, Dennis O
  • Olesen, Morten Salling
  • Padmanabhan, Sandosh
  • Psaty, Bruce M
  • Pattaro, Cristian
  • Ribeiro, Antonio Luiz P
  • Rotter, Jerome I
  • Stricker, Bruno H
  • van der Harst, Pim
  • van Duijn, Cornelia M
  • Verweij, Niek
  • Wilson, James G
  • Orini, Michele
  • Charron, Philippe
  • Watkins, Hugh
  • Kooperberg, Charles
  • Lin, Henry J
  • Wilson, James F
  • Kanters, Jørgen K
  • Sotoodehnia, Nona
  • Mifsud, Borbala
  • Lambiase, Pier D
  • Tereshchenko, Larisa G
  • Munroe, Patricia B

publication date

  • March 14, 2023