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

van der Schouw, Yvonne T.; van der Klauw, Melanie M.; den Hoed, Marcel; van der Harst, Pim; van Duijn, Cornelia M.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.; de Bakker, Paul I. W.; de Geus, Eco J. C.; de Boer, Rudolf A.; de Graaf, Jacqueline; Brundel, Bianca J. J. M.; Peal, David S.; Evans, David M.; Nolte, Ilja M.; Segré, Ayellet V.; Im, Nolte; Handsaker, Robert E.; Hoed, Marcel den; den Hoed, M.; Westra, Harm-Jan; Veldhuisen, Dirk J.; Schouw, Yvonne T.; O’reilly, Paul F.; Zhao, Jing Hua; O’connell, Jeffrey R.; Kim, Young Jin; Mc, Cornelis; O’donnell, Christopher J.; Go, Min Jin; Au, Jackson; Jp, Kemp; Cornalis, M. C.; Eijgelsheim, Mark; Boucher, Gabrielle; Me, Montasser; Ot, Njajou; Gudbjartsson, Daniel; Van Der Harst, P.; Pf, O'Reilly; Hadley, David; Hayward, Caroline; Nj, Timpson; Mf, Feitosa; Kf, Kerr; Igl, Wilmar; Hh, Draisma; Jackson, Anne U.; Pa, Lind; Kutalik, Zoltán; Nc, Onland Moret; Mn, Weedon; Den Heijer, Martin; Esko, Tõnu; Luan, Jian’an; Cm, Albert; Kemp, John P.; Kristiansson, Kati; De, Arking; Pi, de Bakker; Ladenvall, Claes; Lorentzon, Mattias; Jc, Bis; St. Pourcain, Beate; Montasser, May E.; Lind, Penelope A.; Njajou, Omer T.; Sj, Chanock; O'Reilly, Paul F.; Ps, Chines; Sb, Felix; Padmanabhan, Sandosh; Ej, de Geus; Tb, Harris; Rankinen, Tuomo; Al, Hartikainen; Salo, Perttu; Aa, Hicks; As, Havulinna; Tanaka, Toshiko; Zhang, Weihua; Bj, Brundel; Sr, Heckbert; Timpson, Nicholas J.; Draisma, Harmen H. M.; Jj, Hottenga; Cornelis, Marilyn C.; Vitart, Veronique; Feitosa, Mary F.; Mk, Jensen; Kerr, Kathleen F.; Waite, Lindsay; Ja, Kors; Wheeler, William; Mihailov, Evelin; Kt, Khaw; Onland-Moret, N. Charlotte; Song, Ci; Jw, Knowles; As, Kooner; Weedon, Michael N.; Lind, P. A.; Xie, Weijia; Yengo, Loïc; Eg, Lakatta; Ds, Peal; Rn, Luben; Absher, Devin; Kl, Lunetta; Albert, Christine M.; Sn, Lynch; Alonso, Alvaro; De Bakker, P. I. W.; Arking, Dan E.; Im, Leach; Balkau, Beverley; Mr, Markus; Barlassina, Cristina; Benaglio, Paola; Wl, McArdle; Bis, Joshua C.; Bouatia-Naji, Nabila; Sa, McCarroll; Brage, Søren; Doerr, Marcus; Chanock, Stephen J.; Chines, Peter S.; Dörr, Marcus; Chung, Mina; Ka, Miller; Dm, Evans; Darbar, Dawood; Dina, Christian; Se, Medland; Elliott, Paul; Felix, Stephan B.; Gw, Montgomery; De Geus, E. J. C.; Fischer, Krista; Ac, Morrison; Fuchsberger, Christian; Vuml Ller Nurasyid M., M.; Goyette, Philippe; Jr, O'Connell; Gudnason, Vilmundur; Harris, Tamara B.; Pourcain, Beate St; Hartikainen, Anna-Liisa; Havulinna, Aki S.; Cj, O'Donnell; Johansson, Å.; Heckbert, Susan R.; Kk, Ong; Ab, Newman; Hicks, Andrew A.; Hofman, Albert; Heijer, Martin Den; Kääb, Stefan; Holewijn, Suzanne; Kaeaeb, Stefan; Hoogstra-Berends, Femke; Hottenga, Jouke-Jan; Jensen, Majken K.; Harst, Pim van der; Boer, Rudolf A.; Kors, Jan A.; Junttila, Juhani; Kumari, Meena; Milani, Lili; Laiho, Päivi; Kanon, Bart; Ketkar, Shamika; Holm, Hilma; Lakatta, Edward G.; Bm, Psaty; Lundby, Alicia; Langenberg, Claudia; Av, Segrè; Khaw, Kay-Tee; Knowles, Joshua W.; Leusink, Maarten; Liu, Yongmei; Kooner, Angrad S.; Pp, Pramstaller; Luben, Robert N.; Lunetta, Kathryn L.; Dc, Rao; Jh, Zhao; Lynch, Stacey N.; Markus, Marcello R. P.; Marques-Vidal, Pedro; Sm, Ring; Leach, Irene Mateo; Mccarroll, Steven A.; Ej, Rossin; Medland, Sarah E.; Miller, Kathryn A.; Gilst, Wiek H.; Montgomery, Grant W.; Yj, Kim; McArdle, Wendy L.; Morrison, Alanna C.; Ra, Scott; Müller-Nurasyid, Martina; Navarro, Pau; Nelis, Mari; O'Connell, Jeffrey R.; O'Donnell, Christopher J.; Js, Sehmi; Ong, Ken K.; Newman, Anne B.; Mj, Go; Peters, Annette; Jt, Shin; Polasek, Ozren; Pouta, Anneli; Ab, Singleton; Pramstaller, Peter P.; Psaty, Bruce M.; Av, Smith; Rao, Dabeeru C.; Td, Spector; Rossin, Elizabeth J.; Hm, Stringham; Rudan, Diana; Sanna, Serena; Re, Handsaker; Kv, Tarasov; Almgren, Peter; Ring, Susan M.; Scott, Robert A.; Sehmi, Jaban S.; Ag, Uitterlinden; Sharp, Stephen; Shin, Jordan T.; Uitterlinden, André G G.; Sj, Hwang; Johnson, Toby; Singleton, Andrew B.; Smith, Albert V.; Jb, Whitfield; Soranzo, Nicole; Bochud, Murielle; Spector, Tim D.; Sh, Wild; Stewart, Chip; Jc, Witteman; Stringham, Heather M.; Tarasov, Kirill V.; Jf, Wilson; Vandenput, Liesbeth; Hj, Westra; Bakker, P. I. de; Hwang, Shih-Jen; Mueller-Nurasyid, Martina; Whitfield, John B.; Johansson, Åsa; Wijmenga, Cisca; Wild, Sarah H.; Isaacs, Aaron; Jm, Boer; Willemsen, Gonneke; Wilson, James F.; Di, Boomsma; Witteman, Jacqueline C. M.; Wong, Andrew; Wong, Quenna; Ib, Borecki; Jamshidi, Yalda; Cm, van Duijn; Zitting, Paavo; Ng, Forouhi; Boer, Jolanda M. A.; Boomsma, Dorret I.; Bakker, Paul I. W.; Borecki, Ingrid B.; Graaf, Jacqueline de; Van Duijn, C. M.; Johansson, Åsa; Ekelund, Ulf; Forouhi, Nita G.; Ra, Kronmal; Yang, Jian; Froguel, Philippe; Hingorani, Aroon; Ng, Martin; Ingelsson, Erik; Kääb, Stefan; Kivimaki, Mika; Kronmal, Richard A.; Ba, Oostra; Kuh, Diana; Nl, Pedersen; Lind, Lars; Martin, Nicholas G.; Ji, Rotter; Oostra, Ben A.; Wm, Verschuren; Pedersen, Nancy L.; Quertermous, Thomas; Yt, van der Schouw; Rotter, Jerome I.; Dörr, Marcus; Van Der Schouw, Y. T.; Verschuren, W. M. Monique; Duijn, Cornelia M.; Walker, Mark; Do, Arnar; Albanes, Demetrius; Arnar, David O.; Tl, Assimes; Assimes, Themistocles L.; Ra, de Boer; Bandinelli, Stefania; Boehnke, Michael; Wl, Caulfield; De Boer, R. A.; Jc, Chambers; Bouchard, Claude; Wh, van Gilst; Mark Caulfield, W. L.; Chambers, John C.; Caulfield, W. L. Mark; Curhan, Gary; Wc, Hsueh; Cusi, Daniele; Eriksson, Johan; Fb, Hu; Ferrucci, Luigi; Hv, Huikuri; Van Gilst, W. H.; Glorioso, Nicola; Mateo Leach, Irene; De Graaf, J.; Dj, Hunter; Groop, Leif; Gyllensten, Ulf; Mr, Jarvelin; Hsueh, Wen-Chi; Mm, van der Klauw; Hu, Frank B.; Huikuri, Heikki V.; La, Kiemeney; Hunter, David J.; Js, Kooner; Iribarren, Carlos; Isomaa, Bo; Geus, E. J. de; Jarvelin, Marjo-Riitta; Ml, Lokki; Jula, Antti; Kähönen, Mika; Bd, Mitchell; Kiemeney, Lambertus A. L. M.; Ms, Nieminen; Van Der Klauw, M. M.; Kooner, Jaspal S.; Nr, Poulter; Kraft, Peter; Ot, Raitakari; Iacoviello, Licia; Lehtimäki, Terho; Eb, Rimm; Lokki, Marja-Liisa L.; Jd, Rioux; Mitchell, Braxton D.; Navis, Gerjan; Ps, Sever; Nieminen, Markku S.; Ohlsson, Claes; Dc, Shields; Poulter, Neil R.; Ar, Shuldiner; Qi, Lu; Raitakari, Olli T.; Av, Stanton; Rimm, Eric B.; Rp, Stolk; Rioux, John D.; Rizzi, Federica; Dp, Strachan; Rudan, Igor; Salomaa, Veikko; Jc, Tardif; Sever, Peter S.; Dj, van Veldhuisen; Shields, Denis C.; Shuldiner, Alan R.; Ys, Cho; Sinisalo, Juha; Jv, Olsen; Stanton, Alice V.; Stolk, Ronald P.; Pm, Visscher; Strachan, David P.; Tardif, Jean-Claude; Consortium, Global BPgen; Thorsteinsdottir, Unnur; Tuomilehto, Jaako; Consortium, CARDIoGRAM; Van Veldhuisen, D. J.; Kahonen, Mika; Virtamo, Jarmo; Viikari, Jorma; Jr, Thompson; Vollenweider, Peter; Waeber, Gerard; Pr Gwas Consortium, Pfeufer A.; Widen, Elisabeth; Qrs Gwas Consortium, Sotoodehnia N.; Cho, Yoon Shin; Kaab, S.; Olsen, Jesper V.; Visscher, Peter M.; Qt Igc Consortium, Newton Cheh C.; Willer, Cristen; Charge Af, Consortium; Franke, Lude; Erdmann, Jeanette; Pt, Ellinor; Thompson, John R.; Pfeufer, Arne; Bh, Stricker; Sotoodehnia, Nona; Davey Smith, George; Newton-Cheh, Christopher; Ellinor, Patrick T.; Js, Beckmann; Stricker, Bruno H. Ch-H.; Gd, Smith; Metspalu, Andres; Perola, Markus; Nj, Wareham; Beckmann, Jacques S.; Smith, George Davey; Pb, Munroe; Stefansson, Kari; Oc, Sibon; Wareham, Nicholas J.; Munroe, Patricia B.; Dj, Milan; Sibon, Ody C. M.; Geus, Eco J. C.; Milan, David J.; Snieder, Harold; Nj, Samani; Samani, Nilesh J.; Klauw, Melanie M.; Loos, Ruth J. F.; Rj, Loos

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Yvonne van der Schouw
van der Schouw et al., 2013

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Nature Research, Nature Genetics, 6(45), p. 621-631, 2013

DOI: 10.1038/ng.2610

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@article{van der Schouw2013,
  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 = {van der Schouw, Yvonne T. and van der Klauw, Melanie M. and den Hoed, Marcel and van der Harst, Pim and van Duijn, Cornelia M. and van Gilst, Wiek H. and van Veldhuisen, Dirk J. and de Bakker, Paul I. W. and de Geus, Eco J. C. and de Boer, Rudolf A. and de Graaf, Jacqueline and Brundel, Bianca J. J. M. and Peal, David S. and Evans, David M. and Nolte, Ilja M. and Segré, Ayellet V. and Im, Nolte and Handsaker, Robert E. and Hoed, Marcel den and den Hoed, M. and Westra, Harm-Jan and Veldhuisen, Dirk J. and Schouw, Yvonne T. and O’reilly, Paul F. and Zhao, Jing Hua and O’connell, Jeffrey R. and Kim, Young Jin and Mc, Cornelis and O’donnell, Christopher J. and Go, Min Jin and Au, Jackson and Jp, Kemp and Cornalis, M. C. and Eijgelsheim, Mark and Boucher, Gabrielle and Me, Montasser and Ot, Njajou and Gudbjartsson, Daniel and Van Der Harst, P. and Pf, O'Reilly and Hadley, David and Hayward, Caroline and Nj, Timpson and Mf, Feitosa and Kf, Kerr and Igl, Wilmar and Hh, Draisma and Jackson, Anne U. and Pa, Lind and Kutalik, Zoltán and Nc, Onland Moret and Mn, Weedon and Den Heijer, Martin and Esko, Tõnu and Luan, Jian’an and Cm, Albert and Kemp, John P. and Kristiansson, Kati and De, Arking and Pi, de Bakker and Ladenvall, Claes and Lorentzon, Mattias and Jc, Bis and St. Pourcain, Beate and Montasser, May E. and Lind, Penelope A. and Njajou, Omer T. and Sj, Chanock and O'Reilly, Paul F. and Ps, Chines and Sb, Felix and Padmanabhan, Sandosh and Ej, de Geus and Tb, Harris and Rankinen, Tuomo and Al, Hartikainen and Salo, Perttu and Aa, Hicks and As, Havulinna and Tanaka, Toshiko and Zhang, Weihua and Bj, Brundel and Sr, Heckbert and Timpson, Nicholas J. and Draisma, Harmen H. M. and Jj, Hottenga and Cornelis, Marilyn C. and Vitart, Veronique and Feitosa, Mary F. and Mk, Jensen and Kerr, Kathleen F. and Waite, Lindsay and Ja, Kors and Wheeler, William and Mihailov, Evelin and Kt, Khaw and Onland-Moret, N. Charlotte and Song, Ci and Jw, Knowles and As, Kooner and Weedon, Michael N. and Lind, P. A. and Xie, Weijia and Yengo, Loïc and Eg, Lakatta and Ds, Peal and Rn, Luben and Absher, Devin and Kl, Lunetta and Albert, Christine M. and Sn, Lynch and Alonso, Alvaro and De Bakker, P. I. W. and Arking, Dan E. and Im, Leach and Balkau, Beverley and Mr, Markus and Barlassina, Cristina and Benaglio, Paola and Wl, McArdle and Bis, Joshua C. and Bouatia-Naji, Nabila and Sa, McCarroll and Brage, Søren and Doerr, Marcus and Chanock, Stephen J. and Chines, Peter S. and Dörr, Marcus and Chung, Mina and Ka, Miller and Dm, Evans and Darbar, Dawood and Dina, Christian and Se, Medland and Elliott, Paul and Felix, Stephan B. and Gw, Montgomery and De Geus, E. J. C. and Fischer, Krista and Ac, Morrison and Fuchsberger, Christian and Vuml Ller Nurasyid M., M. and Goyette, Philippe and Jr, O'Connell and Gudnason, Vilmundur and Harris, Tamara B. and Pourcain, Beate St and Hartikainen, Anna-Liisa and Havulinna, Aki S. and Cj, O'Donnell and Johansson, Å. and Heckbert, Susan R. and Kk, Ong and Ab, Newman and Hicks, Andrew A. and Hofman, Albert and Heijer, Martin Den and Kääb, Stefan and Holewijn, Suzanne and Kaeaeb, Stefan and Hoogstra-Berends, Femke and Hottenga, Jouke-Jan and Jensen, Majken K. and Harst, Pim van der and Boer, Rudolf A. and Kors, Jan A. and Junttila, Juhani and Kumari, Meena and Milani, Lili and Laiho, Päivi and Kanon, Bart and Ketkar, Shamika and Holm, Hilma and Lakatta, Edward G. and Bm, Psaty and Lundby, Alicia and Langenberg, Claudia and Av, Segrè and Khaw, Kay-Tee and Knowles, Joshua W. and Leusink, Maarten and Liu, Yongmei and Kooner, Angrad S. and Pp, Pramstaller and Luben, Robert N. and Lunetta, Kathryn L. and Dc, Rao and Jh, Zhao and Lynch, Stacey N. and Markus, Marcello R. P. and Marques-Vidal, Pedro and Sm, Ring and Leach, Irene Mateo and Mccarroll, Steven A. and Ej, Rossin and Medland, Sarah E. and Miller, Kathryn A. and Gilst, Wiek H. and Montgomery, Grant W. and Yj, Kim and McArdle, Wendy L. and Morrison, Alanna C. and Ra, Scott and Müller-Nurasyid, Martina and Navarro, Pau and Nelis, Mari and O'Connell, Jeffrey R. and O'Donnell, Christopher J. and Js, Sehmi and Ong, Ken K. and Newman, Anne B. and Mj, Go and Peters, Annette and Jt, Shin and Polasek, Ozren and Pouta, Anneli and Ab, Singleton and Pramstaller, Peter P. and Psaty, Bruce M. and Av, Smith and Rao, Dabeeru C. and Td, Spector and Rossin, Elizabeth J. and Hm, Stringham and Rudan, Diana and Sanna, Serena and Re, Handsaker and Kv, Tarasov and Almgren, Peter and Ring, Susan M. and Scott, Robert A. and Sehmi, Jaban S. and Ag, Uitterlinden and Sharp, Stephen and Shin, Jordan T. and Uitterlinden, André G G. and Sj, Hwang and Johnson, Toby and Singleton, Andrew B. and Smith, Albert V. and Jb, Whitfield and Soranzo, Nicole and Bochud, Murielle and Spector, Tim D. and Sh, Wild and Stewart, Chip and Jc, Witteman and Stringham, Heather M. and Tarasov, Kirill V. and Jf, Wilson and Vandenput, Liesbeth and Hj, Westra and Bakker, P. I. de and Hwang, Shih-Jen and Mueller-Nurasyid, Martina and Whitfield, John B. and Johansson, Åsa and Wijmenga, Cisca and Wild, Sarah H. and Isaacs, Aaron and Jm, Boer and Willemsen, Gonneke and Wilson, James F. and Di, Boomsma and Witteman, Jacqueline C. M. and Wong, Andrew and Wong, Quenna and Ib, Borecki and Jamshidi, Yalda and Cm, van Duijn and Zitting, Paavo and Ng, Forouhi and Boer, Jolanda M. A. and Boomsma, Dorret I. and Bakker, Paul I. W. and Borecki, Ingrid B. and Graaf, Jacqueline de and Van Duijn, C. M. and Johansson, Åsa and Ekelund, Ulf and Forouhi, Nita G. and Ra, Kronmal and Yang, Jian and Froguel, Philippe and Hingorani, Aroon and Ng, Martin and Ingelsson, Erik and Kääb, Stefan and Kivimaki, Mika and Kronmal, Richard A. and Ba, Oostra and Kuh, Diana and Nl, Pedersen and Lind, Lars and Martin, Nicholas G. and Ji, Rotter and Oostra, Ben A. and Wm, Verschuren and Pedersen, Nancy L. and Quertermous, Thomas and Yt, van der Schouw and Rotter, Jerome I. and Dörr, Marcus and Van Der Schouw, Y. T. and Verschuren, W. M. Monique and Duijn, Cornelia M. and Walker, Mark and Do, Arnar and Albanes, Demetrius and Arnar, David O. and Tl, Assimes and Assimes, Themistocles L. and Ra, de Boer and Bandinelli, Stefania and Boehnke, Michael and Wl, Caulfield and De Boer, R. A. and Jc, Chambers and Bouchard, Claude and Wh, van Gilst and Mark Caulfield, W. L. and Chambers, John C. and Caulfield, W. L. Mark and Curhan, Gary and Wc, Hsueh and Cusi, Daniele and Eriksson, Johan and Fb, Hu and Ferrucci, Luigi and Hv, Huikuri and Van Gilst, W. H. and Glorioso, Nicola and Mateo Leach, Irene and De Graaf, J. and Dj, Hunter and Groop, Leif and Gyllensten, Ulf and Mr, Jarvelin and Hsueh, Wen-Chi and Mm, van der Klauw and Hu, Frank B. and Huikuri, Heikki V. and La, Kiemeney and Hunter, David J. and Js, Kooner and Iribarren, Carlos and Isomaa, Bo and Geus, E. J. de and Jarvelin, Marjo-Riitta and Ml, Lokki and Jula, Antti and Kähönen, Mika and Bd, Mitchell and Kiemeney, Lambertus A. L. M. and Ms, Nieminen and Van Der Klauw, M. M. and Kooner, Jaspal S. and Nr, Poulter and Kraft, Peter and Ot, Raitakari and Iacoviello, Licia and Lehtimäki, Terho and Eb, Rimm and Lokki, Marja-Liisa L. and Jd, Rioux and Mitchell, Braxton D. and Navis, Gerjan and Ps, Sever and Nieminen, Markku S. and Ohlsson, Claes and Dc, Shields and Poulter, Neil R. and Ar, Shuldiner and Qi, Lu and Raitakari, Olli T. and Av, Stanton and Rimm, Eric B. and Rp, Stolk and Rioux, John D. and Rizzi, Federica and Dp, Strachan and Rudan, Igor and Salomaa, Veikko and Jc, Tardif and Sever, Peter S. and Dj, van Veldhuisen and Shields, Denis C. and Shuldiner, Alan R. and Ys, Cho and Sinisalo, Juha and Jv, Olsen and Stanton, Alice V. and Stolk, Ronald P. and Pm, Visscher and Strachan, David P. and Tardif, Jean-Claude and Consortium, Global BPgen and Thorsteinsdottir, Unnur and Tuomilehto, Jaako and Consortium, CARDIoGRAM and Van Veldhuisen, D. J. and Kahonen, Mika and Virtamo, Jarmo and Viikari, Jorma and Jr, Thompson and Vollenweider, Peter and Waeber, Gerard and Pr Gwas Consortium, Pfeufer A. and Widen, Elisabeth and Qrs Gwas Consortium, Sotoodehnia N. and Cho, Yoon Shin and Kaab, S. and Olsen, Jesper V. and Visscher, Peter M. and Qt Igc Consortium, Newton Cheh C. and Willer, Cristen and Charge Af, Consortium and Franke, Lude and Erdmann, Jeanette and Pt, Ellinor and Thompson, John R. and Pfeufer, Arne and Bh, Stricker and Sotoodehnia, Nona and Davey Smith, George and Newton-Cheh, Christopher and Ellinor, Patrick T. and Js, Beckmann and Stricker, Bruno H. Ch-H. and Gd, Smith and Metspalu, Andres and Perola, Markus and Nj, Wareham and Beckmann, Jacques S. and Smith, George Davey and Pb, Munroe and Stefansson, Kari and Oc, Sibon and Wareham, Nicholas J. and Munroe, Patricia B. and Dj, Milan and Sibon, Ody C. M. and Geus, Eco J. C. and Milan, David J. and Snieder, Harold and Nj, Samani and Samani, Nilesh J. and Klauw, Melanie M. and Loos, Ruth J. F. and Rj, Loos},
  doi = {10.1038/ng.2610},
  journal = {Nature Genetics},
  month = {apr},
  pages = {621-631},
  title = {Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders},
  url = {http://www.nature.com/articles/ng.2610.pdf},
  volume = {45},
  year = {2013}
}

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

Journal article published in 2013 by Yvonne T. van der Schouw

, Melanie M. van der Klauw, Marcel den Hoed, Pim van der Harst, Cornelia M. van Duijn, Wiek H. van Gilst, Dirk J. van Veldhuisen, Paul I. W. de Bakker, Eco J. C. de Geus, Rudolf A. de Boer, Jacqueline de Graaf, Bianca J. J. M. Brundel, David S. Peal, David M. Evans, Ilja M. Nolte, Ayellet V. Segré, Nolte Im, Robert E. Handsaker, Marcel den Hoed, M. den Hoed, Harm-Jan Westra, Dirk J. Veldhuisen, Yvonne T. Schouw, Paul F. O’reilly, Jing Hua Zhao, Jeffrey R. O’connell, Young Jin Kim, Cornelis Mc, Christopher J. O’donnell, Min Jin Go, Jackson Au, Kemp Jp, M. C. Cornalis, Mark Eijgelsheim, Gabrielle Boucher, Montasser Me, Njajou Ot, Daniel Gudbjartsson

, P. Van Der Harst, O'Reilly Pf, David Hadley, Caroline Hayward, Timpson Nj, Feitosa Mf, Kerr Kf, Wilmar Igl, Draisma Hh, Anne U. Jackson, Lind Pa, Zoltán Kutalik, Onland Moret Nc, Weedon Mn, Martin Den Heijer

, Tõnu Esko

, Jian’an Luan, Albert Cm, John P. Kemp, Kati Kristiansson, Arking De, de Bakker Pi, Claes Ladenvall, Mattias Lorentzon, Bis Jc, Beate St. Pourcain

, May E. Montasser, Penelope A. Lind, Omer T. Njajou, Chanock Sj, Paul F. O'Reilly, Chines Ps, Felix Sb, Sandosh Padmanabhan, de Geus Ej, Harris Tb, Tuomo Rankinen, Hartikainen Al, Perttu Salo, Hicks Aa, Havulinna As, Toshiko Tanaka, Weihua Zhang, Brundel Bj, Heckbert Sr, Nicholas J. Timpson

, Harmen H. M. Draisma, Hottenga Jj, Marilyn C. Cornelis, Veronique Vitart, Mary F. Feitosa, Jensen Mk, Kathleen F. Kerr, Lindsay Waite, Kors Ja, William Wheeler, Evelin Mihailov, Khaw Kt, N. Charlotte Onland-Moret, Ci Song, Knowles Jw, Kooner As, Michael N. Weedon, P. A. Lind

, Weijia Xie, Loïc Yengo, Lakatta Eg, Peal Ds, Luben Rn, Devin Absher, Lunetta Kl, Christine M. Albert, Lynch Sn, Alvaro Alonso, P. I. W. De Bakker, Dan E. Arking, Leach Im, Beverley Balkau, Markus Mr, Cristina Barlassina, Paola Benaglio, McArdle Wl, Joshua C. Bis, Nabila Bouatia-Naji, McCarroll Sa, Søren Brage, Marcus Doerr, Stephen J. Chanock, Peter S. Chines, Marcus Dörr, Mina Chung, Miller Ka, Evans Dm, Dawood Darbar, Christian Dina, Medland Se, Paul Elliott, Stephan B. Felix, Montgomery Gw, E. J. C. De Geus, Krista Fischer, Morrison Ac, Christian Fuchsberger, M. Vuml Ller Nurasyid M., Philippe Goyette, O'Connell Jr, Vilmundur Gudnason, Tamara B. Harris, Beate St Pourcain, Anna-Liisa Hartikainen, Aki S. Havulinna, O'Donnell Cj, Å. Johansson, Susan R. Heckbert, Ong Kk, Newman Ab, Andrew A. Hicks, Albert Hofman, Martin Den Heijer, Stefan Kääb, Suzanne Holewijn, Stefan Kaeaeb, Femke Hoogstra-Berends, Jouke-Jan Hottenga, Majken K. Jensen, Pim van der Harst, Rudolf A. Boer, Jan A. Kors, Juhani Junttila, Meena Kumari, Lili Milani, Päivi Laiho, Bart Kanon, Shamika Ketkar, Hilma Holm, Edward G. Lakatta, Psaty Bm, Alicia Lundby

, Claudia Langenberg, Segrè Av, Kay-Tee Khaw, Joshua W. Knowles, Maarten Leusink, Yongmei Liu, Angrad S. Kooner, Pramstaller Pp, Robert N. Luben

, Kathryn L. Lunetta, Rao Dc, Zhao Jh, Stacey N. Lynch, Marcello R. P. Markus, Pedro Marques-Vidal, Ring Sm, Irene Mateo Leach, Steven A. Mccarroll, Rossin Ej, Sarah E. Medland, Kathryn A. Miller, Wiek H. Gilst, Grant W. Montgomery, Kim Yj, Wendy L. McArdle, Alanna C. Morrison, Scott Ra, Martina Müller-Nurasyid, Pau Navarro

, Mari Nelis, Jeffrey R. O'Connell, Christopher J. O'Donnell, Sehmi Js, Ken K. Ong, Anne B. Newman

, Go Mj, Annette Peters, Shin Jt, Ozren Polasek, Anneli Pouta, Singleton Ab, Peter P. Pramstaller

, Bruce M. Psaty, Smith Av, Dabeeru C. Rao, Spector Td, Elizabeth J. Rossin, Stringham Hm, Diana Rudan, Serena Sanna

, Handsaker Re, Tarasov Kv, Peter Almgren, Susan M. Ring, Robert A. Scott, Jaban S. Sehmi, Uitterlinden Ag, Stephen Sharp, Jordan T. Shin, André G G. Uitterlinden, Hwang Sj, Toby Johnson

, Andrew B. Singleton, Albert V. Smith

, Whitfield Jb, Nicole Soranzo, Murielle Bochud, Tim D. Spector, Wild Sh, Chip Stewart, Witteman Jc, Heather M. Stringham, Kirill V. Tarasov, Wilson Jf, Liesbeth Vandenput, Westra Hj, P. I. de Bakker, Shih-Jen Hwang, Martina Mueller-Nurasyid, John B. Whitfield, Åsa Johansson, Cisca Wijmenga

, Sarah H. Wild, Aaron Isaacs, Boer Jm, Gonneke Willemsen, James F. Wilson, Boomsma Di, Jacqueline C. M. Witteman, Andrew Wong, Quenna Wong, Borecki Ib, Yalda Jamshidi, van Duijn Cm, Paavo Zitting, Forouhi Ng, Jolanda M. A. Boer, Dorret I. Boomsma, Paul I. W. Bakker, Ingrid B. Borecki, Jacqueline de Graaf, C. M. Van Duijn, Åsa Johansson, Ulf Ekelund, Nita G. Forouhi, Kronmal Ra, Jian Yang

, Philippe Froguel, Aroon Hingorani, Martin Ng, Erik Ingelsson, Stefan Kääb, Mika Kivimaki

, Richard A. Kronmal, Oostra Ba, Diana Kuh, Pedersen Nl, Lars Lind, Nicholas G. Martin, Rotter Ji, Ben A. Oostra, Verschuren Wm, Nancy L. Pedersen, Thomas Quertermous, van der Schouw Yt, Jerome I. Rotter, Marcus Dörr, Y. T. Van Der Schouw, W. M. Monique Verschuren, Cornelia M. Duijn, Mark Walker, Arnar Do, Demetrius Albanes, David O. Arnar, Assimes Tl, Themistocles L. Assimes, de Boer Ra, Stefania Bandinelli, Michael Boehnke, Caulfield Wl, R. A. De Boer, Chambers Jc, Claude Bouchard, van Gilst Wh, W. L. Mark Caulfield, John C. Chambers, W. L. Mark Caulfield, Gary Curhan, Hsueh Wc, Daniele Cusi, Johan Eriksson, Hu Fb, Luigi Ferrucci, Huikuri Hv, W. H. Van Gilst, Nicola Glorioso, Irene Mateo Leach, J. De Graaf, Hunter Dj, Leif Groop, Ulf Gyllensten, Jarvelin Mr, Wen-Chi Hsueh, van der Klauw Mm, Frank B. Hu, Heikki V. Huikuri, Kiemeney La, David J. Hunter, Kooner Js, Carlos Iribarren, Bo Isomaa, E. J. de Geus, Marjo-Riitta Jarvelin, Lokki Ml, Antti Jula, Mika Kähönen, Mitchell Bd, Lambertus A. L. M. Kiemeney, Nieminen Ms, M. M. Van Der Klauw, Jaspal S. Kooner, Poulter Nr, Peter Kraft, Raitakari Ot, Licia Iacoviello, Terho Lehtimäki, Rimm Eb, Marja-Liisa L. Lokki, Rioux Jd, Braxton D. Mitchell, Gerjan Navis, Sever Ps, Markku S. Nieminen, Claes Ohlsson, Shields Dc, Neil R. Poulter, Shuldiner Ar, Lu Qi, Olli T. Raitakari, Stanton Av, Eric B. Rimm, Stolk Rp, John D. Rioux, Federica Rizzi, Strachan Dp, Igor Rudan, Veikko Salomaa, Tardif Jc, Peter S. Sever, van Veldhuisen Dj, Denis C. Shields, Alan R. Shuldiner, Cho Ys, Juha Sinisalo, Olsen Jv, Alice V. Stanton

, Ronald P. Stolk, Visscher Pm, David P. Strachan, Jean-Claude Tardif, Global BPgen Consortium, Unnur Thorsteinsdottir, Jaako Tuomilehto, CARDIoGRAM Consortium, D. J. Van Veldhuisen, Mika Kahonen, Jarmo Virtamo, Jorma Viikari, Thompson Jr, Peter Vollenweider, Gerard Waeber, Pfeufer A. Pr Gwas Consortium, Elisabeth Widen, Sotoodehnia N. Qrs Gwas Consortium, Yoon Shin Cho, S. Kaab, Jesper V. Olsen, Peter M. Visscher, Newton Cheh C. Qt Igc Consortium, Cristen Willer, Consortium Charge Af, Lude Franke

, Jeanette Erdmann, Ellinor Pt, John R. Thompson, Arne Pfeufer, Stricker Bh, Nona Sotoodehnia, George Davey Smith, Christopher Newton-Cheh, Patrick T. Ellinor, Beckmann Js, Bruno H. Ch-H. Stricker, Smith Gd, Andres Metspalu, Markus Perola, Wareham Nj, Jacques S. Beckmann, George Davey Smith, Munroe Pb, Kari Stefansson, Sibon Oc, Nicholas J. Wareham, Patricia B. Munroe, Milan Dj, Ody C. M. Sibon, Eco J. C. Geus, David J. Milan, Harold Snieder, Samani Nj, Nilesh J. Samani, Melanie M. Klauw, Ruth J. F. Loos, Loos Rj

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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.

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

Abstract