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

Hum Mol Genet. 2016 May 15;25(10):2093-2103. doi: 10.1093/hmg/ddw058. Epub 2016 Mar 8.


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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Arrhythmias, Cardiac / genetics*
  • Arrhythmias, Cardiac / physiopathology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Brugada Syndrome / genetics*
  • Brugada Syndrome / physiopathology
  • Cardiac Conduction System Disease
  • Death, Sudden, Cardiac / pathology
  • Electrocardiography*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Heart Conduction System / physiopathology
  • Humans
  • Male
  • NAV1.5 Voltage-Gated Sodium Channel / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Repressor Proteins / genetics
  • Shab Potassium Channels / genetics
  • Shal Potassium Channels / genetics


  • Adaptor Proteins, Signal Transducing
  • Basic Helix-Loop-Helix Transcription Factors
  • HEY2 protein, human
  • KCNB1 protein, human
  • KCND3 protein, human
  • NAV1.5 Voltage-Gated Sodium Channel
  • NOS1AP protein, human
  • Repressor Proteins
  • SCN5A protein, human
  • Shab Potassium Channels
  • Shal Potassium Channels