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Journal Articles Nature Communications Year : 2023

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

William Young , Jeffrey Haessler , Jan-Walter Benjamins , Linda Repetto , Jie Yao , Aaron Isaacs , Andrew Harper , Julia Ramirez , Sophie Garnier (1, 2, 3, 4) , Stefan van Duijvenboden , Antoine Baldassari , Maria Pina Concas , Thuyvy Duong , Luisa Foco , Jonas Isaksen , Hao Mei , Raymond Noordam , Casia Nursyifa , Anne Richmond , Meddly Santolalla , Colleen Sitlani , Negin Soroush , Sébastien Thériault , Stella Trompet , Stefanie Aeschbacher , Fariba Ahmadizar , Alvaro Alonso , Jennifer Brody , Archie Campbell , Adolfo Correa , Dawood Darbar , Antonio de Luca , Jean-François Deleuze , Christina Ellervik , Christian Fuchsberger , Anuj Goel , Christopher Grace , Xiuqing Guo , Torben Hansen , Susan Heckbert , Rebecca Jackson , Jan Kors , Maria Fernanda Lima-Costa , Allan Linneberg , Peter Macfarlane , Alanna Morrison , Pau Navarro , David Porteous , Peter Pramstaller , Alexander Reiner , Lorenz Risch , Ulrich Schotten , Xia Shen , Gianfranco Sinagra , Elsayed Soliman , Monika Stoll , Eduardo Tarazona-Santos , Andrew Tinker , Katerina Trajanoska , Eric Villard , Helen Warren , Eric Whitsel , Kerri Wiggins , Dan Arking , Christy Avery , David Conen , Giorgia Girotto , Niels Grarup , Caroline Hayward , J.Wouter Jukema , Dennis Mook-Kanamori , Morten Salling Olesen , Sandosh Padmanabhan , Bruce Psaty , Cristian Pattaro , Antonio Luiz P. Ribeiro , Jerome Rotter , Bruno Stricker , Pim van der Harst , Cornelia van Duijn , Niek Verweij , James Wilson , Michele Orini , Philippe Charron (3, 5, 6, 7, 8) , Hugh Watkins , Charles Kooperberg , Henry Lin , James Wilson , Jørgen Kanters , Nona Sotoodehnia , Borbala Mifsud , Pier Lambiase , Larisa Tereshchenko , Patricia Munroe
William Young
Jeffrey Haessler
  • Function : Author
Jan-Walter Benjamins
Linda Repetto
  • Function : Author
Jie Yao
  • Function : Author
Aaron Isaacs
Andrew Harper
Julia Ramirez
Stefan van Duijvenboden
  • Function : Author
Antoine Baldassari
  • Function : Author
Maria Pina Concas
Thuyvy Duong
  • Function : Author
Luisa Foco
Jonas Isaksen
Hao Mei
  • Function : Author
Raymond Noordam
Casia Nursyifa
  • Function : Author
Anne Richmond
  • Function : Author
Meddly Santolalla
  • Function : Author
Colleen Sitlani
  • Function : Author
Negin Soroush
Sébastien Thériault
  • Function : Author
Stella Trompet
Stefanie Aeschbacher
  • Function : Author
Fariba Ahmadizar
  • Function : Author
Alvaro Alonso
Jennifer Brody
Archie Campbell
Adolfo Correa
Dawood Darbar
Antonio de Luca
  • Function : Author
Jean-François Deleuze
Christina Ellervik
Christian Fuchsberger
Anuj Goel
Christopher Grace
  • Function : Author
Xiuqing Guo
Torben Hansen
Susan Heckbert
Rebecca Jackson
  • Function : Author
Jan Kors
  • Function : Author
Maria Fernanda Lima-Costa
  • Function : Author
Allan Linneberg
Peter Macfarlane
Alanna Morrison
Pau Navarro
David Porteous
Peter Pramstaller
Alexander Reiner
Lorenz Risch
Ulrich Schotten
  • Function : Author
Xia Shen
Gianfranco Sinagra
Elsayed Soliman
Monika Stoll
  • Function : Author
Eduardo Tarazona-Santos
  • Function : Author
Andrew Tinker
Katerina Trajanoska
  • Function : Author
Eric Villard
  • Function : Author
Helen Warren
Eric Whitsel
Kerri Wiggins
Dan Arking
  • Function : Author
Christy Avery
David Conen
  • Function : Author
Giorgia Girotto
Niels Grarup
Caroline Hayward
J.Wouter Jukema
Dennis Mook-Kanamori
  • Function : Author
Morten Salling Olesen
Sandosh Padmanabhan
  • Function : Author
Bruce Psaty
Cristian Pattaro
Antonio Luiz P. Ribeiro
Jerome Rotter
  • Function : Author
Bruno Stricker
  • Function : Author
Pim van der Harst
  • Function : Author
Cornelia van Duijn
Niek Verweij
James Wilson
  • Function : Author
Michele Orini
Hugh Watkins
Charles Kooperberg
Henry Lin
James Wilson
Jørgen Kanters
Nona Sotoodehnia
  • Function : Author
Borbala Mifsud
Pier Lambiase
  • Function : Author
Larisa Tereshchenko
Patricia Munroe

Abstract

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.
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Dates and versions

hal-04028558 , version 1 (14-03-2023)

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William Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, et al.. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease. Nature Communications, 2023, 14 (1), pp.1411. ⟨10.1038/s41467-023-36997-w⟩. ⟨hal-04028558⟩
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