Genetic Architecture of Spatial Electrical Biomarkers for Cardiac Arrhythmia and Relationship with Cardiovascular Disease

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Citation

Young, William J.; Haessler, Jeffrey; Benjamins, Jan W.; Repetto, Linda; Yao, Jie; Isaacs, Aaron J.; Harper, Andrew R.; Ramirez, Julia; Garnier, Sophie; & van Duijvenboden, Stefan, et al. (2023). Genetic Architecture of Spatial Electrical Biomarkers for Cardiac Arrhythmia and Relationship with Cardiovascular Disease. Nature Communications, 14(1), 1411. PMCID: PMC10015012

Abstract

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.

URL

http://dx.doi.org/10.1038/s41467-023-36997-w

Reference Type

Journal Article

Year Published

2023

Journal Title

Nature Communications

Author(s)

Young, William J.
Haessler, Jeffrey
Benjamins, Jan W.
Repetto, Linda
Yao, Jie
Isaacs, Aaron J.
Harper, Andrew R.
Ramirez, Julia
Garnier, Sophie
van Duijvenboden, Stefan
Baldassari, Antoine R.
Concas, Maria Pina
Duong, ThuyVy
Foco, Luisa
Isaksen, Jonas L.
Mei, Hao
Noordam, Raymond
Nursyifa, Casia
Richmond, Anne
Santolalla, Meddly L.
Sitlani, Colleen M.
Soroush, Negin
Thériault, Sébastien
Trompet, Stella
Aeschbacher, Stefanie
Ahmadizar, Fariba
Alonso, Alvaro
Brody, Jennifer A.
Campbell, Archie
Correa, Adolfo
Darbar, Dawood
De Luca, Antonio
Deleuze, Jean-François
Ellervik, Christina
Fuchsberger, Christian
Goel, Anuj
Grace, Christopher
Guo, Xiuqing
Hansen, Torben
Heckbert, Susan R.
Jackson, Rebecca D.
Kors, Jan A.
Lima-Costa, Maria Fernanda
Linneberg, Allan
Macfarlane, Peter W.
Morrison, Alanna C.
Navarro, Pau
Porteous, David J.
Pramstaller, Peter P.
Reiner, Alexander P.
Risch, Lorenz
Schotten, Ulrich
Shen, Xia
Sinagra, Gianfranco
Soliman, Elsayed Z.
Stoll, Monika
Tarazona-Santos, Eduardo
Tinker, Andrew
Trajanoska, Katerina
Villard, Eric
Warren, Helen R.
Whitsel, Eric A.
Wiggins, Kerri L.
Arking, Dan E.
Avery, Christy L.
Conen, David
Girotto, Giorgia
Grarup, Niels
Hayward, Caroline
Jukema, J. Wouter
Mook-Kanamori, Dennis O.
Olesen, Morten S.
Padmanabhan, Sandosh
Psaty, Bruce M.
Pattaro, Cristian
Ribeiro, Antonio Luiz P.
Rotter, Jerome I.
Stricker, Bruno H.
van der Harst, Pim
van Duijn, Cornelia M.
Verweij, Niek
Wilson, James G.
Orini, Michele
Charron, Philippe
Watkins, Hugh
Kooperberg, Charles
Lin, Henry J.
Wilson, James F.
Kanters, Jørgen K.
Sotoodehnia, Nona
Mifsud, Borbala
Lambiase, Pier D.
Tereshchenko, Larisa G.
Munroe, Patricia B.

Article Type

Regular

PMCID

PMC10015012

Data Set/Study

Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium

Continent/Country

Nonspecific

Race/Ethnicity

European Ancestry
Hispanic Ancestry
African Ancestry

ORCiD

Avery - 0000-0002-1044-8162