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ExomeChip-wide analysis of 95 626 individuals identifies 10 novel loci associated with QT and JT intervals.

Circ. Genom. Precis. Med. 11:e001758 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest. METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci. CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Arrhythmias, Cardiac ; Death, Sudden, Cardiac ; Genetics ; Genome ; Humans; Sudden Cardiac Death; General-population; Common Variants; Cohort Profile; N-rap; Design; Health; Epidemiology; Genetics; Hypertension
ISSN (print) / ISBN 2574-8300
e-ISSN 2574-8300
Journal Circulation Genomic and precision medicine
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: e001758 Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Philadelphia, Pa.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)
Institute of Human Genetics (IHG)