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

Young, William J; Haessler, Jeffrey; Benjamins, Jan-Walter; Repetto, Linda; Yao, Jie; Isaacs, Aaron; 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; ... (2023). Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease. Nature communications, 14(1), p. 1411. Nature Publishing Group 10.1038/s41467-023-36997-w

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Risch, Lorenz

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Pubmed Import

Date Deposited:

16 Mar 2023 13:32

Last Modified:

19 Mar 2023 02:15

Publisher DOI:

10.1038/s41467-023-36997-w

PubMed ID:

36918541

BORIS DOI:

10.48350/180194

URI:

https://boris.unibe.ch/id/eprint/180194

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