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. ; Harper, A. R. ; Ramirez, J. (Universidad de Zaragoza) ; Garnier, S. ; van Duijvenboden, S. ; Baldassari, A. R. ; Pina Concas, M. ; 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. ; De Luca, A. ; Deleuze, J. F. ; Ellervik, C. ; Fuchsberger, C. ; Goel, A. ; Grace, C. ; Guo, X. ; 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. ; van der Harst, P. ; van Duijn, C. M. ; 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.

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41467-023-36997-w

Año: 2023

Publicado en: Nature communications 14 (2023), 1411 [16 pp.]
ISSN: 2041-1723

Factor impacto JCR: 14.7 (2023)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 8 / 134 = 0.06 (2023) - Q1 - T1

Factor impacto CITESCORE: 24.9 - Biochemistry, Genetics and Molecular Biology (all) (Q1) - Chemistry (all) (Q1) - Physics and Astronomy (all) (Q1)

Factor impacto SCIMAGO: 4.887 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/786833/EU/GENetics and the Electrocardiogram for predicting Scd rISk/GENESIS
Financiación: info:eu-repo/grantAgreement/EC/H2020/860974/EU/Personalized Therapies for Atrial Fibrillation. A Translational Approach/PersonalizeAF
Financiación: info:eu-repo/grantAgreement/EC/H2020/965286/EU/Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation/MAESTRIA

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Teoría Señal y Comunicac. (Dpto. Ingeniería Electrón.Com.)