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Genetic Basis and Prognostic Value of Exercise QT Dynamics

Van Duijvenboden, S; Ramírez, J; Young, WJ; Mifsud, B; Orini, M; Tinker, A; Munroe, PB; (2020) Genetic Basis and Prognostic Value of Exercise QT Dynamics. Circulation: Genomic and Precision Medicine 10.1161/CIRCGEN.119.002774. (In press). Green open access

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Abstract

Background - Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated. / Methods - QT dynamics during exercise and recovery were derived in 56,643 individuals from UK Biobank without a history of cardiovascular events. Genome-wide association studies (GWAS) were conducted to identify genetic variants and bioinformatics analyses were performed to prioritize candidate genes. The prognostic value of QT dynamics was evaluated for cardiovascular events (death or hospitalization) and all-cause mortality. / Results - Heritability of QT dynamics during exercise and recovery were 10.7% and 5.4% respectively GWASs identified 20 loci, of which four loci included genes implicated in mendelian long QT syndrome. Five loci did not overlap with previously reported resting QT interval loci, candidate genes included KCNQ4 and KIAA1755. Genetic risk scores were not associated with CV events in 357,882 unrelated individuals from UK Biobank. We also did not observe associations of QT dynamics during exercise and recovery with cardiovascular events. Increased QT dynamics during recovery was significantly associated with all-cause mortality in the univariate Cox regression analysis (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.05-1.13, P=2.28 x 10-5), but the association was not significant after adjusting for clinical risk factors. / Conclusions - QT interval dynamics during exercise and recovery are heritable markers but do not carry independent prognostic information for clinical outcomes in the UK Biobank, a population-based cohort. Their prognostic importance may relate to cardiovascular disease cohorts where structural heart disease and/or ischaemia may influence repolarization dynamics. The strong overlap between QT dynamics and resting QT interval loci suggests common biological pathways, however non-overlapping loci suggests alternative mechanisms may exists that underlie QT interval dynamics.

Type: Article
Title: Genetic Basis and Prognostic Value of Exercise QT Dynamics
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCGEN.119.002774
Publisher version: https://doi.org/10.1161/CIRCGEN.119.002774
Language: English
Additional information: Copyright © 2020 The Authors. Circulation Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
URI: https://discovery.ucl.ac.uk/id/eprint/10101481
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