Nature communications, Volume 14, Issue 1, 14 2 2023, Pages 1411 Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease. Young WJ, Haessler J, Benjamins JW, Repetto L, Yao J, Isaacs A, Harper AR, Ramirez J, Garnier S, van Duijvenboden S, Baldassari AR, Concas MP, Duong T, 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 JF, Ellervik C, Fuchsberger C, Goel A, Grace C, Guo X, Hansen T, Heckbert SR, Jackson RD, Kors JA, Lima-Costa MF, 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, Jukema JW, Mook-Kanamori DO, Olesen MS, Padmanabhan S, Psaty BM, Pattaro C, Ribeiro ALP, 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, K

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.

Nat Commun. 2023 3;14(1):1411