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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
Nature Genetics, Volume 46, No. 8, Year 2014
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Description
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. © 2014 Nature America, Inc.
Authors & Co-Authors
Arking, Dan E.
Unknown Affiliation
Pulit, Sara L.
Unknown Affiliation
CROTTI, L.
Unknown Affiliation
Van Der Harst, Pim
Unknown Affiliation
Munroe, Patricia B.
Unknown Affiliation
Koopmann, Tamara T.
Unknown Affiliation
Sotoodehnia, Nona
Unknown Affiliation
Rossin, Elizabeth
Unknown Affiliation
Morley, Michael
Unknown Affiliation
Wang, Xinchen
Unknown Affiliation
Johnson, A. D.
Unknown Affiliation
Lundby, Alicia
Unknown Affiliation
Gudbjartsson, Daníel Fannar
Unknown Affiliation
Noseworthy, Peter A.
Unknown Affiliation
Eijgelsheim, Mark
Unknown Affiliation
Bradford, Yuki
Unknown Affiliation
Tarasov, Kirill V.
Unknown Affiliation
Dörr, Marcus
Unknown Affiliation
Müller-Nurasyid, Martina
Unknown Affiliation
Lahtinen, Annukka M.
Unknown Affiliation
Nolte, Ilja Maria
Unknown Affiliation
Smith, Albert Vernon
Unknown Affiliation
Bis, Joshua C.M.
Unknown Affiliation
Isaacs, Aaron J.
Unknown Affiliation
Newhouse, Stephen J.
Unknown Affiliation
Evans, Daniel S.
Unknown Affiliation
Post, Wendy S.
Unknown Affiliation
Waggott, Daryl M.
Unknown Affiliation
Lyytikäinen, Leo Pekka
Unknown Affiliation
Hicks, Andrew Anthony
Unknown Affiliation
Eisele, Lewin
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Ellinghaus, David
Unknown Affiliation
Hayward, Caroline
Unknown Affiliation
Navarro, Pau
Unknown Affiliation
Ulivi, Sheila
Unknown Affiliation
Tanaka, Toshiko
Unknown Affiliation
Tester, David J.
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Chatel, Stéphanie
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Gustafsson, Stefan
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Kumari, Meena
Unknown Affiliation
Morris, Richard W.
Unknown Affiliation
Naluai, Åsa Torinsson
Unknown Affiliation
Padmanabhan, Sandosh
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Kluttig, Alexander
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Strohmer, Bernhard
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Panayiotou, Andrie G.
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Torres-Español, María
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Knoflach, Michael
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Hubacek, Jaroslav A.
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Slowikowski, Kamil
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Raychaudhuri, Soumya
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Kumar, Runjun
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Harris, Tamara B.
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Launer, Lenore J.
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Shuldiner, Alan R.
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Alonso, Alvaro
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Bader, Joel S.
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Ehret, Georg B.
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Huang, Hailiang
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Kao, Wenhong Linda
Unknown Affiliation
Strait, James B.
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Macfarlane, Peter W.
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Brown, Morris J.
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Caulfield, Mark J.
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Samani, Nilesh J.
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Kronenberg, Florian
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Willeit, Johann
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Smith, Jacqueline Gustav
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Greiser, Karin Halina
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Meyer Zu Schwabedissen, Henriette
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Werdan, Karl
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Carella, Massimo
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Zelante, Leopoldo
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Heckbert, Susan R.
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Psaty, Bruce M.
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Rotter, Jerome I.
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Kolcic, Ivana
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Polašek, Ozren
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Wright, Alan F.
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Griffin, Maura
Unknown Affiliation
Daly, Mark J.
Unknown Affiliation
Arnar, David O.
Unknown Affiliation
Hólm, Hilma
Unknown Affiliation
Thorsteinsdottir, Unnur Arna
Unknown Affiliation
Denny, Joshua C.
Unknown Affiliation
Roden, Dan M.L.
Unknown Affiliation
Zuvich, Rebecca L.
Unknown Affiliation
Emilsson, Valur
Unknown Affiliation
Plump, Andrew S.
Unknown Affiliation
Larson, Martin G.
Unknown Affiliation
O'Donnell, Christopher J.
Unknown Affiliation
Yin, Xiaoyan
Unknown Affiliation
Bobbo, Marco
Unknown Affiliation
d'Adamo, Adamo P.
Unknown Affiliation
Iorio, Anna Maria Aria
Unknown Affiliation
Sinagra, Gianfranco F.
Unknown Affiliation
Carracedo, Ángel M.
Unknown Affiliation
Cummings, Steven R.
Unknown Affiliation
Nalls, Mike A.
Unknown Affiliation
Jula, Antti M.
Unknown Affiliation
Statistics
Citations: 100
Authors: 100
Affiliations: 85
Identifiers
Doi:
10.1038/ng.3014
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Genetics And Genomics
Noncommunicable Diseases