||Heritability of ECG Biomarkers in the Netherlands Twin Registry Measured from Holter ECGs
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||ECG, heritability, human genetics, twins, Holter electrocardiogram
||Introduction: The resting ECG is the most commonly used tool to assess cardiac
electrophysiology. Previous studies have estimated heritability of ECG parameters based
on these snapshots of the cardiac electrical activity. In this study we set out to determine
whether analysis of heart rate specific data from Holter ECGs allows more complete
assessment of the heritability of ECG parameters.
Methods and Results: Holter ECGs were recorded from 221 twin pairs and analyzed
using a multi-parameter beat binning approach. Heart rate dependent estimates of
heritability for QRS duration, QT interval, Tpeak–Tend and Theight were calculated using
structural equation modeling. QRS duration is largely determined by environmental
factors whereas repolarization is primarily genetically determined. Heritability estimates
of both QT interval and Theight were significantly higher when measured from Holter
compared to resting ECGs and the heritability estimate of each was heart rate dependent.
Analysis of the genetic contribution to correlation between repolarization parameters
demonstrated that covariance of individual ECG parameters at different heart rates
overlap but at each specific heart rate there was relatively little overlap in the genetic
determinants of the different repolarization parameters.
Conclusions: Here we present the first study of heritability of repolarization parameters
measured from Holter ECGs. Our data demonstrate that higher heritability can be
estimated from the Holter than the resting ECG and reveals rate dependence in the
genetic—environmental determinants of the ECG that has not previously been tractable.
Future applications include deeper dissection of the ECG of participants with inherited
cardiac electrical disease.