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Region Hovedstaden - en del af Københavns Universitetshospital
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

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  • 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
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  • Michael J Cutler
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  • Martin Gögele
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  • Torben Hansen
  • Susan R Heckbert
  • Paul L Huang
  • Heikki V Huikuri
  • Nina Hutri-Kähönen
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  • 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
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  • 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
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  • Eric A Whitsel
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  • Nona Sotoodehnia
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Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftNature Communications
Vol/bind13
Udgave nummer1
Sider (fra-til)5144
ISSN2041-1722
DOI
StatusUdgivet - 1 sep. 2022

Bibliografisk note

© 2022. The Author(s).

ID: 84600855