Publication type
Journal Article
Authors
- 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
- Daniel F. Gudbjartsson
- Peter A. Noseworthy
- Mark Eijgelsheim
- Yuki Bradford
- Kirill V. Tarasov
- Marcus Dorr
- Martina Muller-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 Lyytikainen
- Andrew A. Hicks
- Lewin Eisele
- David Ellinghaus
- Caroline Hayward
- Pau Navarro
- Sheila Ulivi
- Toshiko Tanaka
- David J. Tester
- Stephanie 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
- J. 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 Polasek
- Alan F. Wright
- Maura Griffin
- Mark J. Daly
- David O. Arnar
- Hilma Holm
- 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 Jockel
- Hagen Kalsch
- Markus M. Nothen
- 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
- Fabiola Del Greco M
- Christian Fuchsberger
- Jeffrey R. O'Connell
- Wai K. Lee
- Graham C. M. Watt
- 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
- Andre G. Uitterlinden
- Jacqueline C. M. Witteman
- Lyudmyla Kedenko
- Claudia Lamina
- Ben A. Oostra
- Goncalo R. Abecasis
- Edward G. Lakatta
- Antonella Mulas
- Marco Orru
- David Schlessinger
- Manuela Uda
- Marcello R. P. Markus
- Uwe Völker
- Harold Snieder
- Timothy D. Spector
- Johan Arnlov
- Lars Lind
- Johan Sundström
- Ann-Christine Syvänen
- Mika Kivimaki
- Mika Kahonen
- 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. Muhleisen
- Peter P. Pramstaller
- Terho J. Lehtimaki
- 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 Kaab
- Aravinda Chakravarti
- Michael J. Ackerman
- Arne Pfeufer
- Paul I. W. de Bakker
- Christopher Newton-Cheh
Publication date
August 15, 2014
Summary:
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 [sim]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.
Published in
Nature Genetics
Volume and page numbers
Volume: 46 , p.826 -836
DOI
http://dx.doi.org/10.1038/ng.3014
ISSN
15461718
Subjects
#522616