Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

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Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. / den Hoed, Marcel; Eijgelsheim, Mark; Esko, Tõnu; Brundel, Bianca J J M; Peal, David S; Evans, David M; Nolte, Ilja M; Segrè, Ayellet V; Holm, Hilma; Handsaker, Robert E; Westra, Harm-Jan; Johnson, Toby; Isaacs, Aaron; Yang, Jian; Lundby, Alicia; Zhao, Jing Hua; Kim, Young Jin; Go, Min Jin; Almgren, Peter; Bochud, Murielle; Boucher, Gabrielle; Cornelis, Marilyn C; Gudbjartsson, Daniel; Hadley, David; van der Harst, Pim; Hayward, Caroline; den Heijer, Martin; Igl, Wilmar; Jackson, Anne U; Kutalik, Zoltán; Luan, Jian'an; Kemp, John P; Kristiansson, Kati; Ladenvall, Claes; Lorentzon, Mattias; Montasser, May E; Njajou, Omer T; O'Reilly, Paul F; Padmanabhan, Sandosh; St Pourcain, Beate; Rankinen, Tuomo; Salo, Perttu; Tanaka, Toshiko; Timpson, Nicholas J; Vitart, Veronique; Waite, Lindsay; Wheeler, William; Zhang, Weihua; Draisma, Harmen H M; Olsen, Jesper V; Global BPgen Consortium.

In: Nature Genetics, Vol. 45, No. 6, 14.04.2013, p. 621-631.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

den Hoed, M, Eijgelsheim, M, Esko, T, Brundel, BJJM, Peal, DS, Evans, DM, Nolte, IM, Segrè, AV, Holm, H, Handsaker, RE, Westra, H-J, Johnson, T, Isaacs, A, Yang, J, Lundby, A, Zhao, JH, Kim, YJ, Go, MJ, Almgren, P, Bochud, M, Boucher, G, Cornelis, MC, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, AU, Kutalik, Z, Luan, J, Kemp, JP, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, ME, Njajou, OT, O'Reilly, PF, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, NJ, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, HHM, Olsen, JV & Global BPgen Consortium 2013, 'Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders', Nature Genetics, vol. 45, no. 6, pp. 621-631. https://doi.org/10.1038/ng.2610

APA

den Hoed, M., Eijgelsheim, M., Esko, T., Brundel, B. J. J. M., Peal, D. S., Evans, D. M., Nolte, I. M., Segrè, A. V., Holm, H., Handsaker, R. E., Westra, H-J., Johnson, T., Isaacs, A., Yang, J., Lundby, A., Zhao, J. H., Kim, Y. J., Go, M. J., Almgren, P., ... Global BPgen Consortium (2013). Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics, 45(6), 621-631. https://doi.org/10.1038/ng.2610

Vancouver

den Hoed M, Eijgelsheim M, Esko T, Brundel BJJM, Peal DS, Evans DM et al. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics. 2013 Apr 14;45(6):621-631. https://doi.org/10.1038/ng.2610

Author

den Hoed, Marcel ; Eijgelsheim, Mark ; Esko, Tõnu ; Brundel, Bianca J J M ; Peal, David S ; Evans, David M ; Nolte, Ilja M ; Segrè, Ayellet V ; Holm, Hilma ; Handsaker, Robert E ; Westra, Harm-Jan ; Johnson, Toby ; Isaacs, Aaron ; Yang, Jian ; Lundby, Alicia ; Zhao, Jing Hua ; Kim, Young Jin ; Go, Min Jin ; Almgren, Peter ; Bochud, Murielle ; Boucher, Gabrielle ; Cornelis, Marilyn C ; Gudbjartsson, Daniel ; Hadley, David ; van der Harst, Pim ; Hayward, Caroline ; den Heijer, Martin ; Igl, Wilmar ; Jackson, Anne U ; Kutalik, Zoltán ; Luan, Jian'an ; Kemp, John P ; Kristiansson, Kati ; Ladenvall, Claes ; Lorentzon, Mattias ; Montasser, May E ; Njajou, Omer T ; O'Reilly, Paul F ; Padmanabhan, Sandosh ; St Pourcain, Beate ; Rankinen, Tuomo ; Salo, Perttu ; Tanaka, Toshiko ; Timpson, Nicholas J ; Vitart, Veronique ; Waite, Lindsay ; Wheeler, William ; Zhang, Weihua ; Draisma, Harmen H M ; Olsen, Jesper V ; Global BPgen Consortium. / Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. In: Nature Genetics. 2013 ; Vol. 45, No. 6. pp. 621-631.

Bibtex

@article{421d8dc019404ed5bc46b894892bf711,
title = "Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders",
abstract = "Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.",
author = "{den Hoed}, Marcel and Mark Eijgelsheim and T{\~o}nu Esko and Brundel, {Bianca J J M} and Peal, {David S} and Evans, {David M} and Nolte, {Ilja M} and Segr{\`e}, {Ayellet V} and Hilma Holm and Handsaker, {Robert E} and Harm-Jan Westra and Toby Johnson and Aaron Isaacs and Jian Yang and Alicia Lundby and Zhao, {Jing Hua} and Kim, {Young Jin} and Go, {Min Jin} and Peter Almgren and Murielle Bochud and Gabrielle Boucher and Cornelis, {Marilyn C} and Daniel Gudbjartsson and David Hadley and {van der Harst}, Pim and Caroline Hayward and {den Heijer}, Martin and Wilmar Igl and Jackson, {Anne U} and Zolt{\'a}n Kutalik and Jian'an Luan and Kemp, {John P} and Kati Kristiansson and Claes Ladenvall and Mattias Lorentzon and Montasser, {May E} and Njajou, {Omer T} and O'Reilly, {Paul F} and Sandosh Padmanabhan and {St Pourcain}, Beate and Tuomo Rankinen and Perttu Salo and Toshiko Tanaka and Timpson, {Nicholas J} and Veronique Vitart and Lindsay Waite and William Wheeler and Weihua Zhang and Draisma, {Harmen H M} and Olsen, {Jesper V} and {Global BPgen Consortium}",
year = "2013",
month = apr,
day = "14",
doi = "10.1038/ng.2610",
language = "English",
volume = "45",
pages = "621--631",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "6",

}

RIS

TY - JOUR

T1 - Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

AU - den Hoed, Marcel

AU - Eijgelsheim, Mark

AU - Esko, Tõnu

AU - Brundel, Bianca J J M

AU - Peal, David S

AU - Evans, David M

AU - Nolte, Ilja M

AU - Segrè, Ayellet V

AU - Holm, Hilma

AU - Handsaker, Robert E

AU - Westra, Harm-Jan

AU - Johnson, Toby

AU - Isaacs, Aaron

AU - Yang, Jian

AU - Lundby, Alicia

AU - Zhao, Jing Hua

AU - Kim, Young Jin

AU - Go, Min Jin

AU - Almgren, Peter

AU - Bochud, Murielle

AU - Boucher, Gabrielle

AU - Cornelis, Marilyn C

AU - Gudbjartsson, Daniel

AU - Hadley, David

AU - van der Harst, Pim

AU - Hayward, Caroline

AU - den Heijer, Martin

AU - Igl, Wilmar

AU - Jackson, Anne U

AU - Kutalik, Zoltán

AU - Luan, Jian'an

AU - Kemp, John P

AU - Kristiansson, Kati

AU - Ladenvall, Claes

AU - Lorentzon, Mattias

AU - Montasser, May E

AU - Njajou, Omer T

AU - O'Reilly, Paul F

AU - Padmanabhan, Sandosh

AU - St Pourcain, Beate

AU - Rankinen, Tuomo

AU - Salo, Perttu

AU - Tanaka, Toshiko

AU - Timpson, Nicholas J

AU - Vitart, Veronique

AU - Waite, Lindsay

AU - Wheeler, William

AU - Zhang, Weihua

AU - Draisma, Harmen H M

AU - Olsen, Jesper V

AU - Global BPgen Consortium

PY - 2013/4/14

Y1 - 2013/4/14

N2 - Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

AB - Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

U2 - 10.1038/ng.2610

DO - 10.1038/ng.2610

M3 - Journal article

C2 - 23583979

VL - 45

SP - 621

EP - 631

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -

ID: 45558358