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. Hirschhorn; Laurie 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; Lifelines Cohort Study

doi:10.1093/hmg/ddw058

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^*, Lifelines Cohort Study

^*Corresponding author voor dit werk

Onderzoeksoutput › Academic › peer review

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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.

Originele taal-2	English
Pagina's (van-tot)	2093-2103
Aantal pagina's	11
Tijdschrift	Human Molecular Genetics
Volume	25
Nummer van het tijdschrift	10
DOI's	https://doi.org/10.1093/hmg/ddw058
Status	Published - 15-mei-2016

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10.1093/hmg/ddw058Licentie: CC BY-NC

Twenty-eight genetic loci associated with ST-T wave amplitudes of the electrocardiogramFinal publisher's version, 631 KBLicentie: CC BY-NC

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Lifelines Biobank
Bakker, S. (Creator), Dotinga, A. (Creator), Vonk, J. M. (Creator), Smidt, N. (Creator), Scholtens, S. (Creator), Swertz, M. (Creator), Wijmenga, C. (Creator), Wolffenbutel, B. H. (Creator), Stolk, R. (Creator), van Zon, S. (Creator), Rosmalen, J. (Creator), Postma, D. S. (Creator), de Boer, R. (Creator), Navis, G. (Creator), Slaets, J. (Creator), Ormel, J. (Creator), van Dijk, F. (Creator) & Bolmer, B. (Data Manager), Lifelines, 2006
https://www.lifelines.nl/ en nog één link, https://catalogue.lifelines.nl/ (minder tonen)
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Verweij, N., Leach, I. M., Isaacs, A., Arking, D. E., Bis, J. C., Pers, T. H., Van den Berg, M. E., Lyytikainen, L.-P., Barnett, P., Wang, X., Soliman, E. Z., Van Duijn, C. M., Kahonen, M., Van Veldhuisen, D. J., Kors, J. A., Raitakari, O. T., Silva, C. T., Lehtimaki, T., Hillege, H. L., ... Lifelines Cohort Study (2016). Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram. Human Molecular Genetics, 25(10), 2093-2103. https://doi.org/10.1093/hmg/ddw058

@article{760e7017546e47978d087b1a243cb3da,

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 = "GENOME-WIDE ASSOCIATION, SUDDEN CARDIAC-ARREST, EARLY REPOLARIZATION, LEAD AVR, PROGNOSTIC VALUE, BRUGADA SYNDROME, COMMON VARIANTS, HEART-FAILURE, INTERVAL, DISEASE",

author = "Niek Verweij and Leach, {Irene Mateo} and Aaron Isaacs and Arking, {Dan E.} and Bis, {Joshua C.} and Pers, {Tune H.} and {Van den Berg}, {Marten E.} and Leo-Pekka Lyytikainen and Phil Barnett and Xinchen Wang and Soliman, {Elsayed Z.} and {Van Duijn}, {Cornelia M.} and Mika Kahonen and {Van Veldhuisen}, {Dirk J.} and Kors, {Jan A.} and Raitakari, {Olli T.} and Silva, {Claudia T.} and Terho Lehtimaki 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 and {Lifelines Cohort Study}",

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",

number = "10",

}

Verweij, N, Leach, IM, Isaacs, A, Arking, DE, Bis, JC, Pers, TH, Van den Berg, ME, Lyytikainen, L-P, Barnett, P, Wang, X, Soliman, EZ, Van Duijn, CM, Kahonen, M, Van Veldhuisen, DJ, Kors, JA, Raitakari, OT, Silva, CT, Lehtimaki, 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 & Lifelines Cohort Study 2016, 'Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram', Human Molecular Genetics, vol. 25, nr. 10, blz. 2093-2103. https://doi.org/10.1093/hmg/ddw058

TY - JOUR

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

AU - Verweij, Niek

AU - Leach, Irene Mateo

AU - Isaacs, Aaron

AU - Arking, Dan E.

AU - Bis, Joshua C.

AU - Pers, Tune H.

AU - Van den Berg, Marten E.

AU - Lyytikainen, Leo-Pekka

AU - Barnett, Phil

AU - Wang, Xinchen

AU - Soliman, Elsayed Z.

AU - Van Duijn, Cornelia M.

AU - Kahonen, Mika

AU - Van Veldhuisen, Dirk J.

AU - Kors, Jan A.

AU - Raitakari, Olli T.

AU - Silva, Claudia T.

AU - Lehtimaki, 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

AU - Lifelines Cohort Study

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 - GENOME-WIDE ASSOCIATION

KW - SUDDEN CARDIAC-ARREST

KW - EARLY REPOLARIZATION

KW - LEAD AVR

KW - PROGNOSTIC VALUE

KW - BRUGADA SYNDROME

KW - COMMON VARIANTS

KW - HEART-FAILURE

KW - INTERVAL

KW - DISEASE

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

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