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 Lyytikäinen; Phil Barnett; Xinchen Wang; Elsayed Z. Soliman; Cornelia M. Van Duijn; Mika Kähönen; Dirk J. Van Veldhuisen; Jan A. Kors; Olli T. Raitakari; Claudia T. Silva; Terho Lehtimäki; 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; Melanie van der Klauw; Gerjan Navis; Hans Ormel; Dirkje Postma; Judith Rosmalen; Joris Slaets; Ronald Stolk; Bruce Wolffenbuttel; Behrooz Alizadeh; Marike Boezen; Marcel Bruinenberg; Noortje Festen; Harold Snieder; Cisca Wijmenga

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 Lyytikäinen, Phil Barnett, Xinchen Wang, Elsayed Z. Soliman, Cornelia M. Van Duijn, Mika Kähönen, Dirk J. Van Veldhuisen, Jan A. Kors, Olli T. Raitakari, Claudia T. Silva, Terho Lehtimäki, 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, Melanie van der Klauw, Gerjan Navis, Hans Ormel, Dirkje Postma, Judith Rosmalen, Joris Slaets, Ronald Stolk, Bruce Wolffenbuttel, Behrooz Alizadeh, Marike Boezen, Marcel Bruinenberg, Noortje Festen, Harold Snieder, Cisca Wijmenga

School of Medicine and Health Sciences

Research output: Contribution to journal › Research Article › peer-review

21 Scopus citations

Abstract

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

Translated title of the contribution	Veintiocho loci genéticos asociados con las amplitudes de onda ST-T del electrocardiograma
Original language	English (US)
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
State	Published - May 15 2016

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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., Lyytikäinen, L. P., Barnett, P., Wang, X., Soliman, E. Z., Van Duijn, C. M., Kähönen, M., Van Veldhuisen, D. J., Kors, J. A., Raitakari, O. T., Silva, C. T., Lehtimäki, T., Hillege, H. L., ... Wijmenga, C. (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{12a5700216954930b1f7ff3cd2a1ae49,

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

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

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 Lyytik{\"a}inen, {Leo Pekka} 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 and Klauw, {Melanie van der} and Gerjan Navis and Hans Ormel and Dirkje Postma and Judith Rosmalen and Joris Slaets and Ronald Stolk and Bruce Wolffenbuttel and Behrooz Alizadeh and Marike Boezen and Marcel Bruinenberg and Noortje Festen and Harold Snieder and Cisca Wijmenga",

year = "2016",

month = may,

day = "15",

doi = "10.1093/hmg/ddw058",

language = "English (US)",

volume = "25",

pages = "2093--2103",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

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Verweij, N, Leach, IM, Isaacs, A, Arking, DE, Bis, JC, Pers, TH, Van Den Berg, ME, Lyytikäinen, LP, 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, Van Der Harst, P, Klauw, MVD, Navis, G, Ormel, H, Postma, D, Rosmalen, J, Slaets, J, Stolk, R, Wolffenbuttel, B, Alizadeh, B, Boezen, M, Bruinenberg, M, Festen, N, Snieder, H & Wijmenga, C 2016, 'Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram', Human Molecular Genetics, vol. 25, no. 10, pp. 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 - 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

AU - Klauw, Melanie van der

AU - Navis, Gerjan

AU - Ormel, Hans

AU - Postma, Dirkje

AU - Rosmalen, Judith

AU - Slaets, Joris

AU - Stolk, Ronald

AU - Wolffenbuttel, Bruce

AU - Alizadeh, Behrooz

AU - Boezen, Marike

AU - Bruinenberg, Marcel

AU - Festen, Noortje

AU - Snieder, Harold

AU - Wijmenga, Cisca

PY - 2016/5/15

Y1 - 2016/5/15

N2 - © The Author 2016. Published by Oxford University Press.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 Author 2016. Published by Oxford University Press.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.

U2 - 10.1093/hmg/ddw058

DO - 10.1093/hmg/ddw058

M3 - Research 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

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