학술논문
Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.
Document Type
article
Author
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
Source
Nature communications. 14(1)
Subject
Language
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.