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

Young, W.J.; Haessler, J.; Benjamins, J.W.; Repetto, L.; Yao, J.; Isaacs, A.; ... ; Munroe, P.B. (2023)

Article / Letter to editor

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. The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.

• All authors: Young, W.J.; Haessler, J.; Benjamins, J.W.; Repetto, L.; Yao, J.; Isaacs, A.; Harper, A.R.; Ramirez, J.; Garnier, S.; Duijvenboden, S. van; Baldassari, A.R.; Concas, M.P.; Duong, T.; Foco, L.; Isaksen, J.L.; Mei, H.; Noordam, R.; Nursyifa, C.; Richmond, A.; Santolalla, M.L.; Sitlani, C.M.; Soroush, N.; Thériault, S.; Trompet, S.; Aeschbacher, S.; Ahmadizar, F.; Alonso, A.; Brody, J.A.; Campbell, A.; Correa, A.; Darbar, D.; Luca, A. de; Deleuze, J.F.; Ellervik, C.; Fuchsberger, C.; Goel, A.; Grace, C.; Guo, X.Q.; Hansen, T.; Heckbert, S.R.; Jackson, R.D.; Kors, J.A.; Lima-Costa, M.F.; Linneberg, A.; Macfarlane, P.W.; Morrison, A.C.; Navarro, P.; Porteous, D.J.; Pramstaller, P.P.; Reiner, A.P.; Risch, L.; Schotten, U.; Shen, X.; Sinagra, G.; Soliman, E.Z.; Stoll, M.; Tarazona-Santos, E.; Tinker, A.; Trajanoska, K.; Villard, E.; Warren, H.R.; Whitsel, E.A.; Wiggins, K.L.; Arking, D.E.; Avery, C.L.; Conen, D.; Girotto, G.; Grarup, N.; Hayward, C.; Jukema, J.W.; Mook-Kanamori, D.O.; Olesen, M.S.; Padmanabhan, S.; Psaty, B.M.; Pattaro, C.; Ribeiro, A.L.P.; Rotter, J.I.; Stricker, B.H.; Harst, P. van der; Duijn, C.M. van; Verweij, N.; Wilson, J.G.; Orini, M.; Charron, P.; Watkins, H.; Kooperberg, C.; Lin, H.J.; Wilson, J.F.; Kanters, J.K.; Sotoodehnia, N.; Mifsud, B.; Lambiase, P.D.; Tereshchenko, L.G.; Munroe, P.B.
• Date: 2023-03-14
• Journal: Nature Communications
• Volume: 14
• Issue: 1
• DOI: doi:10.1038/s41467-023-36997-w
• Link: https://www.nature.com/articles/s41467-023-36997-w