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

den Hoed, M.; 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, 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.; Waite, L.; Wheeler, W.; Zhang, W.; Draisma, H.H.; 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.; 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.; 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.; Jarvelin, 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.; Franke, L.; Erdmann, J.; Erdmann, J.; Thompson, J.R.; Pfeufer, A.; Pfeufer, A.; Sotoodehnia, N.; Sotoodehnia, N.; Newton-Cheh, C.; Newton-Cheh, C.; Ellinor, P.T.; Ellinor, P.T.; Stricker, B.H.; Metspalu, A.; Perola, M.; Beckmann, J.S.; Smith, G.D.; Stefansson, K.; Wareham, N.J.; Munroe, P.B.; Sibon, O.C.; Milan, D.J.; Snieder, H.; Samani, N.J.; Loos, R.J.

doi:10.1038/ng.2610

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

Details

Download: BIB_9C345D77E5E2.P001.pdf (838.53 [Ko])
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Serval ID

serval:BIB_9C345D77E5E2

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature Genetics

Author(s)

den Hoed M., 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 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., Waite L., Wheeler W., Zhang W., Draisma H.H., 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., 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., 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., Jarvelin 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., Franke L., Erdmann J., Erdmann J., Thompson J.R., Pfeufer A., Pfeufer A., Sotoodehnia N., Sotoodehnia N., Newton-Cheh C., Newton-Cheh C., Ellinor P.T., Ellinor P.T., Stricker B.H., Metspalu A., Perola M., Beckmann J.S., Smith G.D., Stefansson K., Wareham N.J., Munroe P.B., Sibon O.C., Milan D.J., Snieder H., Samani N.J., Loos R.J.

Working group(s)

Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, CHARGE-AF Consortium

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

2013

Peer-reviewed

Oui

Volume

Number

Pages

621-631

Language

english

Notes

Publication types: Journal ArticlePublication Status: ppublish

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.

URN

urn:nbn:ch:serval-BIB_9C345D77E5E26

OAI-PMH

oai:serval.unil.ch:BIB_9C345D77E5E2

DOI

10.1038/ng.2610

Pubmed

23583979

Web of science

000319563900009

Create date

25/04/2013 12:11