Faculty, Staff and Student Publications

Authors

William J Young
Najim Lahrouchi
Aaron Isaacs
ThuyVy Duong
Luisa Foco
Farah Ahmed
Jennifer A Brody
Reem Salman
Raymond Noordam
Jan-Walter Benjamins
Jeffrey Haessler
Leo-Pekka Lyytikäinen
Linda Repetto
Maria Pina Concas
Marten E van den Berg
Stefan Weiss
Antoine R Baldassari
Traci M Bartz
James P Cook
Daniel S Evans
Rebecca Freudling
Oliver Hines
Jonas L Isaksen
Honghuang Lin
Hao Mei
Arden Moscati
Martina Müller-Nurasyid
Casia Nursyifa
Yong Qian
Anne Richmond
Carolina Roselli
Kathleen A Ryan
Eduardo Tarazona-Santos
Sébastien Thériault
Stefan van Duijvenboden
Helen R Warren
Jie Yao
Dania Raza
Stefanie Aeschbacher
Gustav Ahlberg
Alvaro Alonso
Laura Andreasen
Joshua C Bis
Eric Boerwinkle
Archie Campbell
Eulalia Catamo
Massimiliano Cocca
Michael J Cutler
Dawood Darbar
Alessandro De Grandi
Antonio De Luca
Jun Ding
Christina Ellervik
Patrick T Ellinor
Stephan B Felix
Philippe Froguel
Christian Fuchsberger
Martin Gögele
Claus Graff
Mariaelisa Graff
Xiuqing Guo
Torben Hansen
Susan R Heckbert
Paul L Huang
Heikki V Huikuri
Nina Hutri-Kähönen
M Arfan Ikram
Rebecca D Jackson
Juhani Junttila
Maryam Kavousi
Jan A Kors
Thiago P Leal
Rozenn N Lemaitre
Henry J Lin
Lars Lind
Allan Linneberg
Simin Liu
Peter W MacFarlane
Massimo Mangino
Thomas Meitinger
Massimo Mezzavilla
Pashupati P Mishra
Rebecca N Mitchell
Nina Mononen
May E Montasser
Alanna C Morrison
Matthias Nauck
Victor Nauffal
Pau Navarro
Kjell Nikus
Guillaume Pare
Kristen K Patton
Giulia Pelliccione
Alan Pittman
David J Porteous
Peter P Pramstaller
Michael H Preuss
Olli T Raitakari
Alexander P Reiner
Antonio Luiz P Ribeiro
Kenneth M Rice
Lorenz Risch
David Schlessinger
Ulrich Schotten
Claudia Schurmann
Xia Shen
M Benjamin Shoemaker
Gianfranco Sinagra
Moritz F Sinner
Elsayed Z Soliman
Monika Stoll
Konstantin Strauch
Kirill Tarasov
Kent D Taylor
Andrew Tinker
Stella Trompet
André Uitterlinden
Uwe Völker
Henry Völzke
Melanie Waldenberger
Lu-Chen Weng
Eric A Whitsel
James G Wilson
Christy L Avery
David Conen
Adolfo Correa
Francesco Cucca
Marcus Dörr
Sina A Gharib
Giorgia Girotto
Niels Grarup
Caroline Hayward
Yalda Jamshidi
Marjo-Riitta Järvelin
J Wouter Jukema
Stefan Kääb
Mika Kähönen
Jørgen K Kanters
Charles Kooperberg
Terho Lehtimäki
Maria Fernanda Lima-Costa
Yongmei Liu
Ruth J F Loos
Steven A Lubitz
Dennis O Mook-Kanamori
Andrew P Morris
Jeffrey R O'Connell
Morten Salling Olesen
Michele Orini
Sandosh Padmanabhan
Cristian Pattaro
Annette Peters
Bruce M Psaty
Jerome I Rotter
Bruno Stricker
Pim van der Harst
Cornelia M van Duijn
Niek Verweij
James F Wilson
Dan E Arking
Julia Ramirez
Pier D Lambiase
Nona Sotoodehnia
Borbala Mifsud
Christopher Newton-Cheh
Patricia B Munroe

Publication Date

9-1-2022

Journal

Nature Communications

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.

Keywords

Arrhythmias, Cardiac, Death, Sudden, Cardiac, Electrocardiography, Genetic Testing, Humans, Male

DOI

10.1038/s41467-022-32821-z

PMID

36050321

PMCID

PMC9436946

PubMedCentral® Posted Date

9-1-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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