Research Repository

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

Arking, DE and Pulit, SL and Crotti, L and Van Der Harst, P and Munroe, PB and Koopmann, TT and Sotoodehnia, N and Rossin, EJ and Morley, M and Wang, X and Johnson, AD and Lundby, A and Gudbjartsson, DF and Noseworthy, PA and Eijgelsheim, M and Bradford, Y and Tarasov, KV and Dörr, M and Müller-Nurasyid, M and Lahtinen, AM and Nolte, IM and Smith, AV and Bis, JC and Isaacs, A and Newhouse, SJ and Evans, DS and Post, WS and Waggott, D and Lyytikäinen, LP and Hicks, AA and Eisele, L and Ellinghaus, D and Hayward, C and Navarro, P and Ulivi, S and Tanaka, T and Tester, DJ and Chatel, S and Gustafsson, S and Kumari, M and Morris, RW and Naluai, AT and Padmanabhan, S and Kluttig, A and Strohmer, B and Panayiotou, AG and Torres, M and Knoflach, M and Hubacek, JA and Slowikowski, K and Raychaudhuri, S and Kumar, RD and Harris, TB and Launer, LJ and Shuldiner, AR and Alonso, A and Bader, JS and Ehret, G and Huang, H and Kao, WHL and Strait, JB and Macfarlane, PW and Brown, M (2014) 'Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.' Nature Genetics, 46 (8). 826 - 836. ISSN 1061-4036

Full text not available from this repository.

Abstract

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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 06 Feb 2015 14:42
Last Modified: 04 Feb 2019 11:16
URI: http://repository.essex.ac.uk/id/eprint/12684

Actions (login required)

View Item View Item