Genetic Basis and Prognostic Value of Exercise QT Dynamics.

Circulation. Genomic and Precision Medicine
Stefan van DuijvenbodenPier D Lambiase

Abstract

Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated. QT dynamics during exercise and recovery were derived in 56 643 individuals from UK Biobank without a history of cardiovascular events. Genome-wide association studies were conducted to identify genetic variants and bioinformatics analyses were performed to prioritize candidate genes. The prognostic value of QT dynamics was evaluated for cardiovascular events (death or hospitalization) and all-cause mortality. Heritability of QT dynamics during exercise and recovery were 10.7% and 5.4%, respectively. Genome-wide association studies identified 20 loci, of which 4 loci included genes implicated in mendelian long-QT syndrome. Five loci did not overlap with previously reported resting QT interval loci; candidate genes included KCNQ4 and KIAA1755. Genetic risk scores were not associated with cardiovascular events in 357 882 unrelated individuals from UK Biobank. We also did not observe associations of QT dynamics during exercise and recovery with cardiovascular events. Increased QT dynamics during recover...Continue Reading

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Citations

Jul 3, 2021·JRSM Cardiovascular Disease·Julia RamírezAndrew Tinker

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Methods Mentioned

BETA
Hi-C

Software Mentioned

QMUL
COLOC

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