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Updated: Mar 24, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram
Niek Verweij1, Irene Mateo Leach2, Aaron Isaacs3
1Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 301 Binney Street, Cambridge, MA 02142, USA Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, The Netherlands.
Abstract:
The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up.
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