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ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals.
- Source :
-
Circulation. Genomic and precision medicine [Circ Genom Precis Med] 2018 Jan; Vol. 11 (1), pp. e001758. - Publication Year :
- 2018
-
Abstract
- 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.<br />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.<br />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.<br /> (© 2018 The Authors.)
- Subjects :
- Antiporters genetics
DNA-Binding Proteins genetics
Electrocardiography
Genome-Wide Association Study
Humans
Long QT Syndrome ethnology
Long QT Syndrome genetics
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Receptors, Calcium-Sensing genetics
Transcription Factors genetics
Exome genetics
Long QT Syndrome diagnosis
Quantitative Trait Loci
Subjects
Details
- Language :
- English
- ISSN :
- 2574-8300
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Circulation. Genomic and precision medicine
- Publication Type :
- Academic Journal
- Accession number :
- 29874175
- Full Text :
- https://doi.org/10.1161/CIRCGEN.117.001758