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Oxford University Press, Human Molecular Genetics, 10(25), p. 2093-2103, 2016

DOI: 10.1093/hmg/ddw058

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Twenty-eight genetic loci associated with ST-T wave amplitudes of the electrocardiogram

Journal article published in 2016 by Marten E. van den Berg, Cornelia M. van Duijn, Dirk J. van Veldhuisen, Wiek H. van Gilst, Rudolf A. de Boer, Xinchen Wang, Paul I. W. de Bakker, Pim van der Harst, Irene Mateo Leach, Aaron Isaacs, Irene Mateo Leach, Dan E. Arking, Joshua C. Bis, Tune H. Pers, Leo-Pekka Lyytikäinen and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.