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

Niek Verweij, Irene Mateo Leach, Aaron Isaacs, Dan E. Arking, Joshua C. Bis, Tune H. Pers, Marten E. Van den Berg, Leo-Pekka Lyytikainen, Phil Barnett, Xinchen Wang, Elsayed Z. Soliman, Cornelia M. Van Duijn, Mika Kahonen, Dirk J. Van Veldhuisen, Jan A. Kors, Olli T. Raitakari, Claudia T. Silva, Terho Lehtimaki, Hans L. Hillege, Joel N. HirschhornLaurie A. Boyer, Wiek H. Van Gilst, Alvaro Alonso, Nona Sotoodehnia, Mark Eijgelsheim, Rudolf A. De Boer, Paul I. W. De Bakker, Lude Franke, Pim Van der Harst*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)2093-2103
JournalHuman Molecular Genetics
Volume25
Issue number10
DOIs
Publication statusPublished - 15 May 2016

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