Pulse lineResearch With Heart Logo

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

TitleTwenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram.
Publication TypeJournal Article
Year of Publication2016
AuthorsVerweij N, Mateo Leach I, Isaacs A, Arking DE, Bis JC, Pers TH, van den Berg ME, Lyytikäinen L-P, Barnett P, Wang X, 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
Secondary Authorsvan der Harst P
Corporate AuthorsLifeLines Cohort Study
JournalHum Mol Genet
Date Published2016 05 15
KeywordsAdaptor Proteins, Signal Transducing, Arrhythmias, Cardiac, Basic Helix-Loop-Helix Transcription Factors, Brugada Syndrome, Cardiac Conduction System Disease, Death, Sudden, Cardiac, Electrocardiography, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Conduction System, Humans, Male, NAV1.5 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Repressor Proteins, Shab Potassium Channels, Shal Potassium Channels

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.

Alternate JournalHum Mol Genet
PubMed ID26962151
PubMed Central IDPMC5062578
Grant ListR01 DK075787 / DK / NIDDK NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States