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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
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Genetic Basis and Prognostic Value of Exercise QT Dynamics
Stefan van Duijvenboden1,2, Julia Ramírez1,2, William J Young2,3
1Institute of Cardiovascular Science, University College London, United Kingdom (S.v.D., J.R., M.O., P.D.L.).
Circulation. Genomic and Precision Medicine
|June 13, 2020
Summary
QT interval dynamics during exercise and recovery are heritable but do not predict cardiovascular events in the general population. Further research is needed in specific patient groups.
Area of Science:
- Cardiovascular genetics
- Clinical electrophysiology
- Population health science
Background:
- Abnormal QT interval responses to heart rate (QT dynamics) are known cardiovascular disease risk predictors.
- The genetic basis and prognostic value of QT dynamics in population-based cohorts remain under-investigated.
Purpose of the Study:
- To investigate the genetic underpinnings of QT dynamics during exercise and recovery.
- To evaluate the prognostic value of QT dynamics for cardiovascular events and all-cause mortality in a large population-based cohort.
Main Methods:
- QT dynamics were analyzed during exercise and recovery in 56,643 UK Biobank participants.
- Genome-wide association studies identified genetic variants, and bioinformatics prioritized candidate genes.
- Prognostic value was assessed for cardiovascular events and all-cause mortality.
Main Results:
- Heritability of QT dynamics was 10.7% (exercise) and 5.4% (recovery).
- Twenty genetic loci were identified, with four linked to long-QT syndrome and five novel loci.
- QT dynamics did not predict cardiovascular events; increased recovery QT dynamics showed a univariate association with all-cause mortality, lost after adjustment.
Conclusions:
- QT interval dynamics are heritable but lack independent prognostic value for clinical outcomes in the general population.
- Prognostic significance may be relevant in patient cohorts with existing cardiovascular disease.
- Shared and distinct genetic pathways exist between QT dynamics and resting QT intervals.
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