UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Genetically-Determined Serum Calcium Levels and Markers of Ventricular Repolarisation: A Mendelian Randomization Study in the UK Biobank

Young, WJ; Warren, HR; Mook-Kanamori, DO; Ramírez, J; van Duijvenboden, S; Orini, M; Tinker, A; ... Noordam, R; + view all (2021) Genetically-Determined Serum Calcium Levels and Markers of Ventricular Repolarisation: A Mendelian Randomization Study in the UK Biobank. Circulation: Genomic and Precision Medicine 10.1161/CIRCGEN.120.003231. (In press). Green open access

[img]
Preview
Text
Lambiase_Genetically-Determined Serum Calcium Levels and Markers of Ventricular Repolarisation_AAM.pdf - Accepted version

Download (1MB) | Preview

Abstract

Background - Electrocardiographic (ECG) markers of ventricular depolarisation and repolarisation are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian Randomization (MR). Methods - Independent lead variants from a newly performed genome-wide association study (GWAS) for serum calcium in >300,000 European-ancestry participants from UK-Biobank were used as instrumental variables. Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT and QRS intervals using an inverse-weighted method in 76,226 participants not contributing to the serum calcium GWAS. Sensitivity analyses including MR-Egger, weighted-median estimator, and MR-PRESSO were performed to test for the presence of horizontal pleiotropy. Results - 205 independent lead calcium-associated variants were used as instrumental variables for MR. A decrease of 0.1 mmol/L serum calcium was associated with longer QT (3.01ms (95% CI 3.99, -2.03) and JT (2.89ms (-3.87, - 1.91) intervals. A weak association was observed for QRS duration (secondary analyses only). Results were concordant in all sensitivity analyses. Conclusions - These analyses support a causal effect of serum calcium levels on ventricular repolarisation, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may therefore directly influence cardiovascular disease risk.

Type: Article
Title: Genetically-Determined Serum Calcium Levels and Markers of Ventricular Repolarisation: A Mendelian Randomization Study in the UK Biobank
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCGEN.120.003231
Publisher version: https://doi.org/10.1161/CIRCGEN.120.003231
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: electrocardiographic intervals, ventricular repolarization
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/10127180
Downloads since deposit
9Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item