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

Authors :
den Hoed, M
Eijgelsheim, M
Esko, T
Brundel, Bj
Peal, Ds
Evans, Dm
Nolte, Im
Segrè, Av
Holm, H
Handsaker, Re
Westra, Hj
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, Hh
Feitosa, Mf
Kerr, Kf
Lind, Pa
Mihailov, E
Onland Moret NC
Song, C
Weedon, Mn
Xie, W
Yengo, L
Absher, D
Albert, Cm
Alonso, A
Arking, De
de Bakker PI
Balkau, B
Barlassina, C
Benaglio, P
Bis, Jc
Bouatia Naji, N
Brage, S
Chanock, Sj
Chines, Ps
Chung, M
Darbar, D
Dina, C
Dörr, M
Elliott, P
Felix, Sb
Fischer, K
Fuchsberger, C
de Geus EJ
Goyette, P
Gudnason, V
Harris, Tb
Hartikainen, Al
Havulinna, As
Heckbert, Sr
Hicks, Aa
Hofman, A
Holewijn, S
Hoogstra Berends, F
Hottenga, Jj
Jensen, Mk
Johansson, A
Junttila, J
Kääb, S
Kanon, B
Ketkar, S
Khaw, Kt
Knowles, Jw
Kooner, As
Kors, Ja
Kumari, M
Milani, L
Laiho, P
Lakatta, Eg
Langenberg, C
Leusink, M
Liu, Y
Luben, Rn
Lunetta, Kl
Lynch, Sn
Markus, Mr
Marques Vidal, P
Mateo Leach, I
Mcardle, Wl
Mccarroll, Sa
Medland, Se
Miller, Ka
Montgomery, Gw
Morrison, Ac
Müller Nurasyid, M
Navarro, P
Nelis, M
O'Connell, Jr
O'Donnell, Cj
Ong, Kk
Newman, Ab
Peters, A
Polasek, O
Pouta, A
Pramstaller, Pp
Psaty, Bm
Rao, Dc
Ring, Sm
Rossin, Ej
Rudan, D
Sanna, S
Scott, Ra
Sehmi, Js
Sharp, S
Shin, Jt
Singleton, Ab
Smith, Av
Soranzo, N
Spector, Td
Stewart, C
Stringham, Hm
Tarasov, Kv
Uitterlinden, Ag
Vandenput, L
Hwang, Sj
Whitfield, Jb
Wijmenga, C
Wild, Sh
Willemsen, G
Wilson, Jf
Witteman, Jc
Wong, A
Wong, Q
Jamshidi, Y
Zitting, P
Boer, Jm
Boomsma, Di
Borecki, Ib
van Duijn CM
Ekelund, U
Forouhi, Ng
Froguel, P
Hingorani, A
Ingelsson, E
Kivimaki, M
Kronmal, Ra
Kuh, D
Lind, L
Martin, Ng
Oostra, Ba
Pedersen, Nl
Quertermous, T
Rotter, Ji
van der Schouw YT
Verschuren, Wm
Walker, M
Albanes, D
Arnar, Do
Assimes, Tl
Bandinelli, S
Boehnke, M
de Boer RA
Bouchard, C
Caulfield, Wl
Chambers, Jc
Curhan, G
Cusi, D
Eriksson, J
Ferrucci, L
van Gilst WH
Glorioso, N
de Graaf, J
Groop, L
Gyllensten, U
Hsueh, Wc
Hu, Fb
Huikuri, Hv
Hunter, Dj
Iribarren, C
Isomaa, B
Jarvelin, Mr
Jula, A
Kähönen, M
Kiemeney, La
van der Klauw MM
Kooner, Js
Kraft, P
Iacoviello, Licia
Lehtimäki, T
Lokki, Ml
Mitchell, Bd
Navis, G
Nieminen, Ms
Ohlsson, C
Poulter, Nr
Qi, L
Raitakari, Ot
Rimm, Eb
Rioux, Jd
Rizzi, F
Rudan, I
Salomaa, V
Sever, Ps
Shields, Dc
Shuldiner, Ar
Sinisalo, J
Stanton, Av
Stolk, Rp
Strachan, Dp
Tardif, Jc
Thorsteinsdottir, U
Tuomilehto, J
van Veldhuisen DJ
Virtamo, J
Viikari, J
Vollenweider, P
Waeber, G
Widen, E
Cho, Ys
Olsen, Jv
Visscher, Pm
Willer, C
Franke, L
Global BPgen Consortium
Cardiogram, Consortium
Erdmann, J
Thompson, Jr
PR GWAS Consortium
Pfeufer, A
QRS GWAS Consortium
Sotoodehnia, N
QT IGC Consortium
Newton Cheh, C
CHARGE AF Consortium
Ellinor, Pt
Stricker, Bh
Metspalu, A
Perola, M
Beckmann, Js
Smith, Gd
Stefansson, K
Wareham, Nj
Munroe, Pb
Sibon, Oc
Milan, Dj
Snieder, H
Samani, Nj
Loos, R. J.
Global BPgen Consortium
CARDIoGRAM Consortium
PR GWAS Consortium
QRS GWAS Consortium
QT-IGC Consortium
CHARGE-AF Consortium
Biological Psychology
Neuroscience Campus Amsterdam - Neurobiology of Mental Health
EMGO+ - Lifestyle, Overweight and Diabetes
Neuroscience Campus Amsterdam - Brain Imaging Technology
Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease
Humane Biologie
Epidemiology
Public Health
Clinical Genetics
Surgery
Medical Informatics
Internal Medicine
NCA - Brain mechanisms in health and disease
NCA - Neurobiology of mental health
ICaR - Circulation and metabolism
EMGO - Lifestyle, overweight and diabetes
NCA - Brain imaging technology
ACS - Heart failure & arrhythmias
Physiology
Internal medicine
Cardiovascular Centre (CVC)
Vascular Ageing Programme (VAP)
Life Course Epidemiology (LCE)
Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Lifestyle Medicine (LM)
Groningen Kidney Center (GKC)
Molecular Neuroscience and Ageing Research (MOLAR)
Stem Cell Aging Leukemia and Lymphoma (SALL)
Source :
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, Bochud, M, Boucher, G, Cornelis, M C, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, A U, Kutalik, Z, Luan, J, Kemp, J P, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, M E, Njajou, O T, O'Reilly, P F, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, N J, Vitart, V, Navarro, P, Polasek, O, Wild, S H & Wilson, J F & Rudan, I 2013, ' Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders ', Nature Genetics, vol. 45, no. 6, pp. 621-. https://doi.org/10.1038/ng.2610, Nature Genetics, vol. 45, no. 6, pp. 621-631, Nature Genetics, 45(6), 621-631. Nature Publishing Group, Nature Genetics, 45(6), 621-31. Nature Publishing Group, Nature Genetics, 45, 621-31, Nature Genetics, 45(6), 621-+. Nature Publishing Group, Nature Genetics, 45, 6, pp. 621-31, den Hoed, M A H, Eijgelsheim, M, Esko, T, Brundel, B J, 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, L, Lundby, A, Zhao, J H, Kim, Y J, Go, M J, Almgren, P, Bochud, M, Boucher, G, Cornelis, M C, Gudbjartsson, D F, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, A U, Kutalik, Z, Luan, J, Kemp, J P, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, M E, Njajou, O T, O'Reilly, P F, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, N J, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, H H M, Feitosa, M F, Kerr, K F, Lind, P A, Mihailov, E, Onland-Moret, N C, Song, C, Weedon, M N, Xie, W, Yengo, L, Absher, D, Albert, C M, Alonso, A, Arking, D E, de Bakker, P I, Balkau, B, Barlassina, C, Benaglio, P, Bis, J C, Bouatia-Naji, N, Brage, S, Chanock, S J, Chines, P S, Chung, M, Darbar, D, Dina, C, Dörr, M, Elliott, P, Felix, S B, Fischer, K, Fuchsberger, C, de Geus, E J C, Goyette, P, Gudnason, V, Harris, T B, Hartikainen, A L, Havulinna, A S, Heckbert, S R, Hicks, A A, Hofman, A, Holewijn, S, Hoogstra-Berends, F, Hottenga, J J, Jensen, M K, Johansson, A, Junttila, J, Kääb, S, Kanon, B, Ketkar, S, Khaw, K T, Knowles, J W, Kooner, A S, Kors, J A, Kumari, M, Milani, L, Laiho, P, Lakatta, E G, Langenberg, C, Leusink, M, Liu, Y, Luben, R N, Lunetta, K L, Lynch, S N, Markus, M R, Marques-Vidal, P, Mateo Leach, I, McArdle, W L, McCarroll, S A, Medland, S E, Miller, K A, Montgomery, G W, Morrison, A C, Müller-Nurasyid, M, Navarro, P, Nelis, M, O'Connell, J R, O'Donnell, C J, Ong, K K, Newman, A B, Peters, A, Polasek, O, Pouta, A, Pramstaller, P P, Psaty, B M, Rao, D C, Ring, S M, Rossin, E J, Rudan, D, Sanna, S, Scott, R A, Sehmi, J S, Sharp, S, Shin, J T, Singleton, A B, Smith, A V, Soranzo, N, Spector, T D, Stewart, C, Stringham, H M, Tarasov, K V, Uitterlinden, A G, Vandenput, L, Hwang, S J, Whitfield, J B, Wijmenga, C, Wild, S H, Willemsen, G, Wilson, J F, Witteman, J C, Wong, A, Wong, Q, Jamshidi, Y, Zitting, P, Boer, J M, Boomsma, D I, Borecki, I B, van Duijn, C M, Ekelund, U, Forouhi, N G, Froguel, P, Hingorani, A D, Ingelsson, E, Kivimaki, M, Kronmal, R A, Kuh, D, Lind, L, Martin, N G, Oostra, B A, Pedersen, N L, Quertermous, T, Rotter, J I, van der Schouw, Y T, Verschuren, W M, Walker, M, Albanes, D, Arnar, D O, Assimes, T L, Bandinelli, S, Boehnke, M, de Boer, R A, Bouchard, C, Caulfield, W L, Chambers, J C, Curhan, G, Cusi, D, Eriksson, J, Ferrucci, L, van Gilst, W H, Glorioso, N, de Graaf, J, Groop, L, Gyllensten, U, Hsueh, W C, Hu, F B, Huikuri, H V, Hunter, D J, Iribarren, C, Isomaa, B, Järvelin, M R, Jula, A, Kähönen, M, Kiemeney, L A, van der Klauw, M M, Kooner, J S, Kraft, P, Iacoviello, L, Lehtimäki, T, Lokki, M L, Mitchell, B D, Navis, G, Nieminen, M S, Ohlsson, C, Poulter, N R, Qi, L, Raitakari, O T, Rimm, E B, Rioux, J D, Rizzi, F, Rudan, I, Salomaa, V, Sever, P S, Shields, D C, Shuldiner, A R, Sinisalo, J, Stanton, A V, Stolk, R P, Strachan, D P, Tardif, J C, Thorsteinsdottir, U, Tuomilehto, J, van Veldhuisen, D J, Virtamo, J, Viikari, J, Vollenweider, P, Waeber, G, Widen, E, Cho, Y S, Olsen, J V, Visscher, P M, Willer, C J, Franke, L, Erdmann, J, Thompson, J R, Pfeufer, A, Sotoodehnia, N, Newton-Cheh, C, Ellinor, P T, Stricker, B H C, Metspalu, A, Perola, M, Beckmann, J S, Smith, G D, Stefansson, K, Wareham, N J, Munroe, P B, Sibon, O C M, Milan, D J, Snieder, H, Samani, N J & Loos, R J 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, Nature Genetics
Publication Year :
2013
Publisher :
Nature Publishing Group, 2013.

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. © 2013 Nature America, Inc. All rights reserved.

Details

Language :
English
ISSN :
10614036 and 15461718
Database :
OpenAIRE
Journal :
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, Bochud, M, Boucher, G, Cornelis, M C, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, A U, Kutalik, Z, Luan, J, Kemp, J P, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, M E, Njajou, O T, O'Reilly, P F, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, N J, Vitart, V, Navarro, P, Polasek, O, Wild, S H & Wilson, J F & Rudan, I 2013, ' Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders ', Nature Genetics, vol. 45, no. 6, pp. 621-. https://doi.org/10.1038/ng.2610, Nature Genetics, vol. 45, no. 6, pp. 621-631, Nature Genetics, 45(6), 621-631. Nature Publishing Group, Nature Genetics, 45(6), 621-31. Nature Publishing Group, Nature Genetics, 45, 621-31, Nature Genetics, 45(6), 621-+. Nature Publishing Group, Nature Genetics, 45, 6, pp. 621-31, den Hoed, M A H, Eijgelsheim, M, Esko, T, Brundel, B J, 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, L, Lundby, A, Zhao, J H, Kim, Y J, Go, M J, Almgren, P, Bochud, M, Boucher, G, Cornelis, M C, Gudbjartsson, D F, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, A U, Kutalik, Z, Luan, J, Kemp, J P, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, M E, Njajou, O T, O'Reilly, P F, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, N J, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, H H M, Feitosa, M F, Kerr, K F, Lind, P A, Mihailov, E, Onland-Moret, N C, Song, C, Weedon, M N, Xie, W, Yengo, L, Absher, D, Albert, C M, Alonso, A, Arking, D E, de Bakker, P I, Balkau, B, Barlassina, C, Benaglio, P, Bis, J C, Bouatia-Naji, N, Brage, S, Chanock, S J, Chines, P S, Chung, M, Darbar, D, Dina, C, Dörr, M, Elliott, P, Felix, S B, Fischer, K, Fuchsberger, C, de Geus, E J C, Goyette, P, Gudnason, V, Harris, T B, Hartikainen, A L, Havulinna, A S, Heckbert, S R, Hicks, A A, Hofman, A, Holewijn, S, Hoogstra-Berends, F, Hottenga, J J, Jensen, M K, Johansson, A, Junttila, J, Kääb, S, Kanon, B, Ketkar, S, Khaw, K T, Knowles, J W, Kooner, A S, Kors, J A, Kumari, M, Milani, L, Laiho, P, Lakatta, E G, Langenberg, C, Leusink, M, Liu, Y, Luben, R N, Lunetta, K L, Lynch, S N, Markus, M R, Marques-Vidal, P, Mateo Leach, I, McArdle, W L, McCarroll, S A, Medland, S E, Miller, K A, Montgomery, G W, Morrison, A C, Müller-Nurasyid, M, Navarro, P, Nelis, M, O'Connell, J R, O'Donnell, C J, Ong, K K, Newman, A B, Peters, A, Polasek, O, Pouta, A, Pramstaller, P P, Psaty, B M, Rao, D C, Ring, S M, Rossin, E J, Rudan, D, Sanna, S, Scott, R A, Sehmi, J S, Sharp, S, Shin, J T, Singleton, A B, Smith, A V, Soranzo, N, Spector, T D, Stewart, C, Stringham, H M, Tarasov, K V, Uitterlinden, A G, Vandenput, L, Hwang, S J, Whitfield, J B, Wijmenga, C, Wild, S H, Willemsen, G, Wilson, J F, Witteman, J C, Wong, A, Wong, Q, Jamshidi, Y, Zitting, P, Boer, J M, Boomsma, D I, Borecki, I B, van Duijn, C M, Ekelund, U, Forouhi, N G, Froguel, P, Hingorani, A D, Ingelsson, E, Kivimaki, M, Kronmal, R A, Kuh, D, Lind, L, Martin, N G, Oostra, B A, Pedersen, N L, Quertermous, T, Rotter, J I, van der Schouw, Y T, Verschuren, W M, Walker, M, Albanes, D, Arnar, D O, Assimes, T L, Bandinelli, S, Boehnke, M, de Boer, R A, Bouchard, C, Caulfield, W L, Chambers, J C, Curhan, G, Cusi, D, Eriksson, J, Ferrucci, L, van Gilst, W H, Glorioso, N, de Graaf, J, Groop, L, Gyllensten, U, Hsueh, W C, Hu, F B, Huikuri, H V, Hunter, D J, Iribarren, C, Isomaa, B, Järvelin, M R, Jula, A, Kähönen, M, Kiemeney, L A, van der Klauw, M M, Kooner, J S, Kraft, P, Iacoviello, L, Lehtimäki, T, Lokki, M L, Mitchell, B D, Navis, G, Nieminen, M S, Ohlsson, C, Poulter, N R, Qi, L, Raitakari, O T, Rimm, E B, Rioux, J D, Rizzi, F, Rudan, I, Salomaa, V, Sever, P S, Shields, D C, Shuldiner, A R, Sinisalo, J, Stanton, A V, Stolk, R P, Strachan, D P, Tardif, J C, Thorsteinsdottir, U, Tuomilehto, J, van Veldhuisen, D J, Virtamo, J, Viikari, J, Vollenweider, P, Waeber, G, Widen, E, Cho, Y S, Olsen, J V, Visscher, P M, Willer, C J, Franke, L, Erdmann, J, Thompson, J R, Pfeufer, A, Sotoodehnia, N, Newton-Cheh, C, Ellinor, P T, Stricker, B H C, Metspalu, A, Perola, M, Beckmann, J S, Smith, G D, Stefansson, K, Wareham, N J, Munroe, P B, Sibon, O C M, Milan, D J, Snieder, H, Samani, N J & Loos, R J 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, Nature Genetics
Accession number :
edsair.doi.dedup.....f3f091499ff4331cd37912032e3ea160