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

TitleGenetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.
Publication TypeJournal Article
Year of Publication2023
AuthorsYoung, WJ, Haessler, J, Benjamins, J-W, Repetto, L, Yao, J, Isaacs, A, Harper, AR, Ramirez, J, Garnier, S, Van Duijvenboden, S, Baldassari, AR, Concas, MPina, Duong, TV, Foco, L, Isaksen, JL, Mei, H, Noordam, R, Nursyifa, C, Richmond, A, Santolalla, ML, Sitlani, CM, Soroush, N, Thériault, S, Trompet, S, Aeschbacher, S, Ahmadizar, F, Alonso, A, Brody, JA, Campbell, A, Correa, A, Darbar, D, De Luca, A, Deleuze, J-F, Ellervik, C, Fuchsberger, C, Goel, A, Grace, C, Guo, X, Hansen, T, Heckbert, SR, Jackson, RD, Kors, JA, Lima-Costa, MFernanda, Linneberg, A, Macfarlane, PW, Morrison, AC, Navarro, P, Porteous, DJ, Pramstaller, PP, Reiner, AP, Risch, L, Schotten, U, Shen, X, Sinagra, G, Soliman, EZ, Stoll, M, Tarazona-Santos, E, Tinker, A, Trajanoska, K, Villard, E, Warren, HR, Whitsel, EA, Wiggins, KL, Arking, DE, Avery, CL, Conen, D, Girotto, G, Grarup, N, Hayward, C, J Jukema, W, Mook-Kanamori, DO, Olesen, MSalling, Padmanabhan, S, Psaty, BM, Pattaro, C, Ribeiro, ALuiz P, Rotter, JI, Stricker, BH, van der Harst, P, van Duijn, CM, Verweij, N, Wilson, JG, Orini, M, Charron, P, Watkins, H, Kooperberg, C, Lin, HJ, Wilson, JF, Kanters, JK, Sotoodehnia, N, Mifsud, B, Lambiase, PD, Tereshchenko, LG, Munroe, PB
JournalNat Commun
Date Published2023 Mar 14
KeywordsArrhythmias, Cardiac, Atrioventricular Block, Biomarkers, Cardiovascular Diseases, Electrocardiography, Genome-Wide Association Study, Humans, Risk Factors
Abstract<p>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.</p>
Alternate JournalNat Commun
PubMed ID36918541
PubMed Central IDPMC10015012
Grant ListK24 HL148521 / HL / NHLBI NIH HHS / United States
R01 HL118277 / HL / NHLBI NIH HHS / United States
R56 HL118277 / HL / NHLBI NIH HHS / United States
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