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

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

doi:10.1038/s41467-023-36997-w

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

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

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

Original language	English
Article number	1411
Journal	Nature Communications
Volume	14
Issue number	1
Number of pages	16
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-023-36997-w
Publication status	Published - 14 Mar 2023

Bibliographical note

Keywords

Humans
Cardiovascular Diseases/genetics
Atrioventricular Block
Genome-Wide Association Study
Risk Factors
Arrhythmias, Cardiac/genetics
Electrocardiography/methods
Biomarkers

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FulltextFinal published version, 3.14 MBLicence: CC BY

Cite this

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., Foco, L., Isaksen, J. L., Mei, H., Noordam, R., Nursyifa, C., Richmond, A., ... Munroe, P. B. (2023). Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease. Nature Communications, 14(1), [1411]. https://doi.org/10.1038/s41467-023-36997-w

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; 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 Salling; 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.

In: Nature Communications, Vol. 14, No. 1, 1411, 14.03.2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Young, WJ, Haessler, J, Benjamins, J-W, 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, J-F, 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, Kanters, JK, Sotoodehnia, N, Mifsud, B, Lambiase, PD, Tereshchenko, LG & Munroe, PB 2023, 'Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease', Nature Communications, vol. 14, no. 1, 1411. https://doi.org/10.1038/s41467-023-36997-w

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 ; 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 Salling ; 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. / Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease. In: Nature Communications. 2023 ; Vol. 14, No. 1.

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title = "Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease",

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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T1 - Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

AU - Young, William J

AU - Haessler, Jeffrey

AU - Benjamins, Jan-Walter

AU - Repetto, Linda

AU - Yao, Jie

AU - Isaacs, Aaron

AU - Harper, Andrew R

AU - Ramirez, Julia

AU - Garnier, Sophie

AU - van Duijvenboden, Stefan

AU - Baldassari, Antoine R

AU - Concas, Maria Pina

AU - Duong, ThuyVy

AU - Foco, Luisa

AU - Isaksen, Jonas L

AU - Mei, Hao

AU - Noordam, Raymond

AU - Nursyifa, Casia

AU - Richmond, Anne

AU - Santolalla, Meddly L

AU - Sitlani, Colleen M

AU - Soroush, Negin

AU - Thériault, Sébastien

AU - Trompet, Stella

AU - Aeschbacher, Stefanie

AU - Ahmadizar, Fariba

AU - Alonso, Alvaro

AU - Brody, Jennifer A

AU - Campbell, Archie

AU - Correa, Adolfo

AU - Darbar, Dawood

AU - De Luca, Antonio

AU - Deleuze, Jean-François

AU - Ellervik, Christina

AU - Fuchsberger, Christian

AU - Goel, Anuj

AU - Grace, Christopher

AU - Guo, Xiuqing

AU - Hansen, Torben

AU - Heckbert, Susan R

AU - Jackson, Rebecca D.

AU - Kors, Jan A

AU - Lima-Costa, Maria Fernanda

AU - Linneberg, Allan

AU - Macfarlane, Peter W

AU - Morrison, Alanna C

AU - Navarro, Pau

AU - Porteous, David J

AU - Pramstaller, Peter P

AU - Reiner, Alexander P

AU - Risch, Lorenz

AU - Schotten, Ulrich

AU - Shen, Xia

AU - Sinagra, Gianfranco

AU - Soliman, Elsayed Z

AU - Stoll, Monika

AU - Tarazona-Santos, Eduardo

AU - Tinker, Andrew

AU - Trajanoska, Katerina

AU - Villard, Eric

AU - Warren, Helen R

AU - Whitsel, Eric A

AU - Wiggins, Kerri L

AU - Arking, Dan E

AU - Avery, Christy L

AU - Conen, David

AU - Girotto, Giorgia

AU - Grarup, Niels

AU - Hayward, Caroline

AU - Jukema, J Wouter

AU - Mook-Kanamori, Dennis O

AU - Olesen, Morten Salling

AU - Padmanabhan, Sandosh

AU - Psaty, Bruce M

AU - Pattaro, Cristian

AU - Ribeiro, Antonio Luiz P

AU - Rotter, Jerome I

AU - Stricker, Bruno H

AU - van der Harst, Pim

AU - van Duijn, Cornelia M

AU - Verweij, Niek

AU - Wilson, James G

AU - Orini, Michele

AU - Charron, Philippe

AU - Watkins, Hugh

AU - Kooperberg, Charles

AU - Lin, Henry J

AU - Wilson, James F

AU - Kanters, Jørgen K

AU - Sotoodehnia, Nona

AU - Mifsud, Borbala

AU - Lambiase, Pier D

AU - Tereshchenko, Larisa G

AU - Munroe, Patricia B

PY - 2023/3/14

Y1 - 2023/3/14

N2 - 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.

AB - 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.

KW - Humans

KW - Cardiovascular Diseases/genetics

KW - Atrioventricular Block

KW - Genome-Wide Association Study

KW - Risk Factors

KW - Arrhythmias, Cardiac/genetics

KW - Electrocardiography/methods

KW - Biomarkers

U2 - 10.1038/s41467-023-36997-w

DO - 10.1038/s41467-023-36997-w

M3 - Journal article

C2 - 36918541

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1411

ER -