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

doi:10.1093/hmg/ddw058

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

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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.

Original language	English
Pages (from-to)	2093-2103
Number of pages	11
Journal	Human molecular genetics
Volume	25
Issue number	10
DOIs	https://doi.org/10.1093/hmg/ddw058
Publication status	Published - 15 May 2016

Keywords

Adaptor Proteins, Signal Transducing/genetics
Arrhythmias, Cardiac/genetics
Basic Helix-Loop-Helix Transcription Factors/genetics
Brugada Syndrome/genetics
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

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10.1093/hmg/ddw058

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title = "Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram",

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.",

keywords = "Adaptor Proteins, Signal Transducing/genetics, Arrhythmias, Cardiac/genetics, Basic Helix-Loop-Helix Transcription Factors/genetics, Brugada Syndrome/genetics, 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",

author = "Niek Verweij and {Mateo Leach}, Irene and Aaron Isaacs and Arking, {Dan E} and Bis, {Joshua C} and Pers, {Tune H} and {Van Den Berg}, {Marten E} and Leo-Pekka Lyytik{\"a}inen and Phil Barnett and Xinchen Wang and Soliman, {Elsayed Z} and {Van Duijn}, {Cornelia M} and Mika K{\"a}h{\"o}nen and {Van Veldhuisen}, {Dirk J} and Kors, {Jan A} and Raitakari, {Olli T} and Silva, {Claudia T} and Terho Lehtim{\"a}ki and Hillege, {Hans L} and Hirschhorn, {Joel N} and Boyer, {Laurie A} and {Van Gilst}, {Wiek H} and Alvaro Alonso and Nona Sotoodehnia and Mark Eijgelsheim and {De Boer}, {Rudolf A} and {De Bakker}, {Paul I W} and Lude Franke and {Van Der Harst}, Pim",

note = "{\textcopyright} The Author 2016. Published by Oxford University Press.",

year = "2016",

month = may,

day = "15",

doi = "10.1093/hmg/ddw058",

language = "English",

volume = "25",

pages = "2093--2103",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

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T1 - Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram

AU - Verweij, Niek

AU - Mateo Leach, Irene

AU - Isaacs, Aaron

AU - Arking, Dan E

AU - Bis, Joshua C

AU - Pers, Tune H

AU - Van Den Berg, Marten E

AU - Lyytikäinen, Leo-Pekka

AU - Barnett, Phil

AU - Wang, Xinchen

AU - Soliman, Elsayed Z

AU - Van Duijn, Cornelia M

AU - Kähönen, Mika

AU - Van Veldhuisen, Dirk J

AU - Kors, Jan A

AU - Raitakari, Olli T

AU - Silva, Claudia T

AU - Lehtimäki, Terho

AU - Hillege, Hans L

AU - Hirschhorn, Joel N

AU - Boyer, Laurie A

AU - Van Gilst, Wiek H

AU - Alonso, Alvaro

AU - Sotoodehnia, Nona

AU - Eijgelsheim, Mark

AU - De Boer, Rudolf A

AU - De Bakker, Paul I W

AU - Franke, Lude

AU - Van Der Harst, Pim

N1 - © The Author 2016. Published by Oxford University Press.

PY - 2016/5/15

Y1 - 2016/5/15

N2 - 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.

AB - 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.

KW - Adaptor Proteins, Signal Transducing/genetics

KW - Arrhythmias, Cardiac/genetics

KW - Basic Helix-Loop-Helix Transcription Factors/genetics

KW - Brugada Syndrome/genetics

KW - Cardiac Conduction System Disease

KW - Death, Sudden, Cardiac/pathology

KW - Electrocardiography

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Heart Conduction System/physiopathology

KW - Humans

KW - Male

KW - NAV1.5 Voltage-Gated Sodium Channel/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Repressor Proteins/genetics

KW - Shab Potassium Channels/genetics

KW - Shal Potassium Channels/genetics

U2 - 10.1093/hmg/ddw058

DO - 10.1093/hmg/ddw058

M3 - Article

C2 - 26962151

SN - 0964-6906

VL - 25

SP - 2093

EP - 2103

JO - Human molecular genetics

JF - Human molecular genetics

IS - 10

ER -

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

Abstract

Keywords

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