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Common Genetic Variants Modulate the Electrocardiographic Tpeak-to-Tend Interval.

Abstract：

:Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic risk, and Tpe changes with heart rate are even stronger predictors. However, our understanding of the electrophysiological mechanisms supporting these risk factors is limited. We conducted genome-wide association studies (GWASs) for resting Tpe and Tpe response to exercise and recovery in ∼30,000 individuals, followed by replication in independent samples (∼42,000 for resting Tpe and ∼22,000 for Tpe response to exercise and recovery), all from UK Biobank. Fifteen and one single-nucleotide variants for resting Tpe and Tpe response to exercise, respectively, were formally replicated. In a full dataset GWAS, 13 further loci for resting Tpe, 1 for Tpe response to exercise and 1 for Tpe response to exercise were genome-wide significant (p ≤ 5 × 10-8). Sex-specific analyses indicated seven additional loci. In total, we identify 32 loci for resting Tpe, 3 for Tpe response to exercise and 3 for Tpe response to recovery modulating ventricular repolarization, as well as cardiac conduction and contraction. Our findings shed light on the genetic basis of resting Tpe and Tpe response to exercise and recovery, unveiling plausible candidate genes and biological mechanisms underlying ventricular excitability.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Ramírez J,van Duijvenboden S,Young WJ,Orini M,Lambiase PD,Munroe PB,Tinker A

doi

10.1016/j.ajhg.2020.04.009

subject

Has Abstract

pub_date

2020-06-04 00:00:00

pages

764-778

issue

6

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(20)30118-X

journal_volume

106

pub_type

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