Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram.
Verweij N., Mateo Leach I., Isaacs A., Arking DE., Bis JC., Pers TH., Van Den Berg ME., Lyytikäinen L-P., Barnett P., Wang X., LifeLines Cohort Study None., Soliman EZ., Van Duijn CM., Kähönen M., Van Veldhuisen DJ., Kors JA., Raitakari OT., Silva CT., Lehtimäki T., Hillege HL., Hirschhorn JN., Boyer LA., Van Gilst WH., Alonso A., Sotoodehnia N., Eijgelsheim M., De Boer RA., De Bakker PIW., Franke L., Van Der Harst P.
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.