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.; Garnier S.; van Duijvenboden S.; Baldassari A.R.; Concas M.P.; Duong T.V.; 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. · Nature Communications (2023) · DOI: 10.1038/s41467-023-36997-w

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.

Instituciones: Universidad Peruana Cayetano Heredia