Lund University is celebrating 350 years. Read more on lunduniversity.lu.se

Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

Author:
  • Dan E Arking
  • Sara L Pulit
  • Lia Crotti
  • Pim van der Harst
  • Patricia B Munroe
  • Tamara T Koopmann
  • Nona Sotoodehnia
  • Elizabeth J Rossin
  • Michael Morley
  • Xinchen Wang
  • Andrew D Johnson
  • Alicia Lundby
  • Daníel F Gudbjartsson
  • Peter A Noseworthy
  • Mark Eijgelsheim
  • Yuki Bradford
  • Kirill V Tarasov
  • Marcus Dörr
  • Martina Müller-Nurasyid
  • Annukka M Lahtinen
  • Ilja M Nolte
  • Albert Vernon Smith
  • Joshua C Bis
  • Aaron Isaacs
  • Stephen J Newhouse
  • Daniel S Evans
  • Wendy S Post
  • Daryl Waggott
  • Leo-Pekka Lyytikäinen
  • Andrew A Hicks
  • Lewin Eisele
  • David Ellinghaus
  • Caroline Hayward
  • Pau Navarro
  • Sheila Ulivi
  • Toshiko Tanaka
  • David J Tester
  • Stéphanie Chatel
  • Stefan Gustafsson
  • Meena Kumari
  • Richard W Morris
  • Asa T Naluai
  • Sandosh Padmanabhan
  • Alexander Kluttig
  • Bernhard Strohmer
  • Andrie G Panayiotou
  • Maria Torres
  • Michael Knoflach
  • Jaroslav A Hubacek
  • Kamil Slowikowski
  • Soumya Raychaudhuri
  • Runjun D Kumar
  • Tamara B Harris
  • Lenore J Launer
  • Alan R Shuldiner
  • Alvaro Alonso
  • Joel S Bader
  • Georg Ehret
  • Hailiang Huang
  • W H Linda Kao
  • James B Strait
  • Peter W Macfarlane
  • Morris Brown
  • Mark J Caulfield
  • Nilesh J Samani
  • Florian Kronenberg
  • Johann Willeit
  • Gustav Smith
  • Karin H Greiser
  • Henriette Meyer Zu Schwabedissen
  • Karl Werdan
  • Massimo Carella
  • Leopoldo Zelante
  • Susan R Heckbert
  • Bruce M Psaty
  • Jerome I Rotter
  • Ivana Kolcic
  • Ozren Polašek
  • Alan F Wright
  • Maura Griffin
  • Mark J Daly
  • David O Arnar
  • Hilma Hólm
  • Unnur Thorsteinsdottir
  • Joshua C Denny
  • Dan M Roden
  • Rebecca L Zuvich
  • Valur Emilsson
  • Andrew S Plump
  • Martin G Larson
  • Christopher J O'Donnell
  • Xiaoyan Yin
  • Marco Bobbo
  • Adamo P D'Adamo
  • Annamaria Iorio
  • Gianfranco Sinagra
  • Angel Carracedo
  • Steven R Cummings
  • Michael A Nalls
  • Antti Jula
  • Kimmo K Kontula
  • Annukka Marjamaa
  • Lasse Oikarinen
  • Markus Perola
  • Kimmo Porthan
  • Raimund Erbel
  • Per Hoffmann
  • Karl-Heinz Jöckel
  • Hagen Kälsch
  • Markus M Nöthen
  • Marcel den Hoed
  • Ruth J F Loos
  • Dag S Thelle
  • Christian Gieger
  • Thomas Meitinger
  • Siegfried Perz
  • Annette Peters
  • Hanna Prucha
  • Moritz F Sinner
  • Melanie Waldenberger
  • Rudolf A de Boer
  • Lude Franke
  • Pieter A van der Vleuten
  • Britt Maria Beckmann
  • Eimo Martens
  • Abdennasser Bardai
  • Nynke Hofman
  • Arthur A M Wilde
  • Elijah R Behr
  • Chrysoula Dalageorgou
  • John R Giudicessi
  • Argelia Medeiros-Domingo
  • Julien Barc
  • Florence Kyndt
  • Vincent Probst
  • Alice Ghidoni
  • Roberto Insolia
  • Robert M Hamilton
  • Stephen W Scherer
  • Jeffrey Brandimarto
  • Kenneth Margulies
  • Christine E Moravec
  • NN Fabiola
  • Christian Fuchsberger
  • Jeffrey R O'Connell
  • Wai K Lee
  • Graham C M Watt
  • Harry Campbell
  • Sarah H Wild
  • Nour E El Mokhtari
  • Norbert Frey
  • Folkert W Asselbergs
  • Irene Mateo Leach
  • Gerjan Navis
  • Maarten P van den Berg
  • Dirk J van Veldhuisen
  • Manolis Kellis
  • Bouwe P Krijthe
  • Oscar H Franco
  • Albert Hofman
  • Jan A Kors
  • André G Uitterlinden
  • Jacqueline C M Witteman
  • Lyudmyla Kedenko
  • Claudia Lamina
  • Ben A Oostra
  • Gonçalo R Abecasis
  • Edward G Lakatta
  • Antonella Mulas
  • Marco Orrú
  • David Schlessinger
  • Manuela Uda
  • Marcello R P Markus
  • Uwe Völker
  • Harold Snieder
  • Timothy D Spector
  • Johan Arnlöv
  • Lars Lind
  • Johan Sundström
  • Ann-Christine Syvänen
  • Mika Kivimaki
  • Mika Kähönen
  • Nina Mononen
  • Olli T Raitakari
  • Jorma S Viikari
  • Vera Adamkova
  • Stefan Kiechl
  • Maria Brion
  • Andrew N Nicolaides
  • Bernhard Paulweber
  • Johannes Haerting
  • Anna F Dominiczak
  • Fredrik Nyberg
  • Peter H Whincup
  • Aroon D Hingorani
  • Jean-Jacques Schott
  • Connie R Bezzina
  • Erik Ingelsson
  • Luigi Ferrucci
  • Paolo Gasparini
  • James F Wilson
  • Igor Rudan
  • Andre Franke
  • Thomas W Mühleisen
  • Peter P Pramstaller
  • Terho J Lehtimäki
  • Andrew D Paterson
  • Afshin Parsa
  • Yongmei Liu
  • Cornelia M van Duijn
  • David S Siscovick
  • Vilmundur Gudnason
  • Yalda Jamshidi
  • Veikko Salomaa
  • Stephan B Felix
  • Serena Sanna
  • Marylyn D Ritchie
  • Bruno H Stricker
  • Kari Stefansson
  • Laurie A Boyer
  • Thomas P Cappola
  • Jesper V Olsen
  • Kasper Lage
  • Peter J Schwartz
  • Stefan Kääb
  • Aravinda Chakravarti
  • Michael J Ackerman
  • Arne Pfeufer
  • Paul I W de Bakker
  • Christopher Newton-Cheh
Publishing year: 2014
Language: English
Pages: 826-836
Publication/Series: Nature Genetics
Volume: 46
Issue: 8
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Keywords

  • Cardiac and Cardiovascular Systems

Other

Published
  • ISSN: 1546-1718
E-mail: gustav.smith [at] med.lu.se

Associate professor

Cardiology

+46 46 17 26 33

D1232C

32

Research project participant

Cardiovascular Epigenetics

32

Research project participant

Heart Failure and Mechanical Support

32

Project manager

Molecular Epidemiology and Cardiology

+46 46 17 26 33

32

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00