Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Research output: Contribution to journalJournal articlepeer-review

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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways. / Young, William J; Lahrouchi, Najim; Isaacs, Aaron; Duong, ThuyVy; Foco, Luisa; Ahmed, Farah; Brody, Jennifer A; Salman, Reem; Noordam, Raymond; Benjamins, Jan-Walter; Haessler, Jeffrey; Lyytikäinen, Leo-Pekka; Repetto, Linda; Concas, Maria Pina; van den Berg, Marten E; Weiss, Stefan; Baldassari, Antoine R; Bartz, Traci M; Cook, James P; Evans, Daniel S; Freudling, Rebecca; Hines, Oliver; Isaksen, Jonas L; Lin, Honghuang; Mei, Hao; Moscati, Arden; Müller-Nurasyid, Martina; Nursyifa, Casia; Qian, Yong; Richmond, Anne; Roselli, Carolina; Ryan, Kathleen A; Tarazona-Santos, Eduardo; Thériault, Sébastien; van Duijvenboden, Stefan; Warren, Helen R; Yao, Jie; Raza, Dania; Aeschbacher, Stefanie; Ahlberg, Gustav; Andreasen, Laura; Ellervik, Christina; Hansen, Torben; Jackson, Rebecca D; Lind, Lars; Linneberg, Allan; Grarup, Niels; Kanters, Jørgen K; Loos, Ruth J F; Olesen, Morten Salling; CHARGE Consortium.

In: Nature Communications, Vol. 13, No. 1, 5144, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Young, WJ, Lahrouchi, N, Isaacs, A, Duong, T, Foco, L, Ahmed, F, Brody, JA, Salman, R, Noordam, R, Benjamins, J-W, Haessler, J, Lyytikäinen, L-P, Repetto, L, Concas, MP, van den Berg, ME, Weiss, S, Baldassari, AR, Bartz, TM, Cook, JP, Evans, DS, Freudling, R, Hines, O, Isaksen, JL, Lin, H, Mei, H, Moscati, A, Müller-Nurasyid, M, Nursyifa, C, Qian, Y, Richmond, A, Roselli, C, Ryan, KA, Tarazona-Santos, E, Thériault, S, van Duijvenboden, S, Warren, HR, Yao, J, Raza, D, Aeschbacher, S, Ahlberg, G, Andreasen, L, Ellervik, C, Hansen, T, Jackson, RD, Lind, L, Linneberg, A, Grarup, N, Kanters, JK, Loos, RJF, Olesen, MS & CHARGE Consortium 2022, 'Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways', Nature Communications, vol. 13, no. 1, 5144. https://doi.org/10.1038/s41467-022-32821-z

APA

Young, W. J., Lahrouchi, N., Isaacs, A., Duong, T., Foco, L., Ahmed, F., Brody, J. A., Salman, R., Noordam, R., Benjamins, J-W., Haessler, J., Lyytikäinen, L-P., Repetto, L., Concas, M. P., van den Berg, M. E., Weiss, S., Baldassari, A. R., Bartz, T. M., Cook, J. P., ... CHARGE Consortium (2022). Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways. Nature Communications, 13(1), [5144]. https://doi.org/10.1038/s41467-022-32821-z

Vancouver

Young WJ, Lahrouchi N, Isaacs A, Duong T, Foco L, Ahmed F et al. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways. Nature Communications. 2022;13(1). 5144. https://doi.org/10.1038/s41467-022-32821-z

Author

Young, William J ; Lahrouchi, Najim ; Isaacs, Aaron ; Duong, ThuyVy ; Foco, Luisa ; Ahmed, Farah ; Brody, Jennifer A ; Salman, Reem ; Noordam, Raymond ; Benjamins, Jan-Walter ; Haessler, Jeffrey ; Lyytikäinen, Leo-Pekka ; Repetto, Linda ; Concas, Maria Pina ; van den Berg, Marten E ; Weiss, Stefan ; Baldassari, Antoine R ; Bartz, Traci M ; Cook, James P ; Evans, Daniel S ; Freudling, Rebecca ; Hines, Oliver ; Isaksen, Jonas L ; Lin, Honghuang ; Mei, Hao ; Moscati, Arden ; Müller-Nurasyid, Martina ; Nursyifa, Casia ; Qian, Yong ; Richmond, Anne ; Roselli, Carolina ; Ryan, Kathleen A ; Tarazona-Santos, Eduardo ; Thériault, Sébastien ; van Duijvenboden, Stefan ; Warren, Helen R ; Yao, Jie ; Raza, Dania ; Aeschbacher, Stefanie ; Ahlberg, Gustav ; Andreasen, Laura ; Ellervik, Christina ; Hansen, Torben ; Jackson, Rebecca D ; Lind, Lars ; Linneberg, Allan ; Grarup, Niels ; Kanters, Jørgen K ; Loos, Ruth J F ; Olesen, Morten Salling ; CHARGE Consortium. / Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{3820deec5d2646e0966225a08082257a,
title = "Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways",
abstract = "The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.",
author = "Young, {William J} and Najim Lahrouchi and Aaron Isaacs and ThuyVy Duong and Luisa Foco and Farah Ahmed and Brody, {Jennifer A} and Reem Salman and Raymond Noordam and Jan-Walter Benjamins and Jeffrey Haessler and Leo-Pekka Lyytik{\"a}inen and Linda Repetto and Concas, {Maria Pina} and {van den Berg}, {Marten E} and Stefan Weiss and Baldassari, {Antoine R} and Bartz, {Traci M} and Cook, {James P} and Evans, {Daniel S} and Rebecca Freudling and Oliver Hines and Isaksen, {Jonas L} and Honghuang Lin and Hao Mei and Arden Moscati and Martina M{\"u}ller-Nurasyid and Casia Nursyifa and Yong Qian and Anne Richmond and Carolina Roselli and Ryan, {Kathleen A} and Eduardo Tarazona-Santos and S{\'e}bastien Th{\'e}riault and {van Duijvenboden}, Stefan and Warren, {Helen R} and Jie Yao and Dania Raza and Stefanie Aeschbacher and Gustav Ahlberg and Laura Andreasen and Christina Ellervik and Torben Hansen and Jackson, {Rebecca D} and Lars Lind and Allan Linneberg and Niels Grarup and Kanters, {J{\o}rgen K} and Loos, {Ruth J F} and Olesen, {Morten Salling} and {CHARGE Consortium}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-32821-z",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

AU - Young, William J

AU - Lahrouchi, Najim

AU - Isaacs, Aaron

AU - Duong, ThuyVy

AU - Foco, Luisa

AU - Ahmed, Farah

AU - Brody, Jennifer A

AU - Salman, Reem

AU - Noordam, Raymond

AU - Benjamins, Jan-Walter

AU - Haessler, Jeffrey

AU - Lyytikäinen, Leo-Pekka

AU - Repetto, Linda

AU - Concas, Maria Pina

AU - van den Berg, Marten E

AU - Weiss, Stefan

AU - Baldassari, Antoine R

AU - Bartz, Traci M

AU - Cook, James P

AU - Evans, Daniel S

AU - Freudling, Rebecca

AU - Hines, Oliver

AU - Isaksen, Jonas L

AU - Lin, Honghuang

AU - Mei, Hao

AU - Moscati, Arden

AU - Müller-Nurasyid, Martina

AU - Nursyifa, Casia

AU - Qian, Yong

AU - Richmond, Anne

AU - Roselli, Carolina

AU - Ryan, Kathleen A

AU - Tarazona-Santos, Eduardo

AU - Thériault, Sébastien

AU - van Duijvenboden, Stefan

AU - Warren, Helen R

AU - Yao, Jie

AU - Raza, Dania

AU - Aeschbacher, Stefanie

AU - Ahlberg, Gustav

AU - Andreasen, Laura

AU - Ellervik, Christina

AU - Hansen, Torben

AU - Jackson, Rebecca D

AU - Lind, Lars

AU - Linneberg, Allan

AU - Grarup, Niels

AU - Kanters, Jørgen K

AU - Loos, Ruth J F

AU - Olesen, Morten Salling

AU - CHARGE Consortium

N1 - © 2022. The Author(s).

PY - 2022

Y1 - 2022

N2 - The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

AB - The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

U2 - 10.1038/s41467-022-32821-z

DO - 10.1038/s41467-022-32821-z

M3 - Journal article

C2 - 36050321

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5144

ER -

ID: 318427558