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

Research output: Contribution to journalArticle


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 Tonu Esko and Brundel, {Bianca J. J. M.} and Peal, {David S.} and Evans, {David M.} and Nolte, {Ilja M.} and Segre, {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 Zoltan 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 Pourcain, {Beate St.} 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 Feitosa, {Mary F.} and Kerr, {Kathleen F.} and Lind, {Penelope A.} and Evelin Mihailov and Onland-Moret, {N. Charlotte} and Ci Song and Weedon, {Michael N.} and Weijia Xie and Loic Yengo and Devin Absher and Albert, {Christine M.} and Alvaro Alonso and Arking, {Dan E.} and {de Bakker}, {Paul I. W.} and Beverley Balkau and Cristina Barlassina and Paola Benaglio and Bis, {Joshua C.} and Nabila Bouatia-Naji and Soren Brage and Chanock, {Stephen J.} and Chines, {Peter S.} and Mina Chung and Dawood Darbar and Christian Dina and Marcus Doerr and Paul Elliott and Felix, {Stephan B.} and Krista Fischer and Christian Fuchsberger and {de Geus}, {Eco J. C.} and Philippe Goyette and Vilmundur Gudnason and Harris, {Tamara B.} and Anna-Liisa Hartikainen and Havulinna, {Aki S.} and Heckbert, {Susan R.} and Hicks, {Andrew A.} and Albert Hofman and Suzanne Holewijn and Femke Hoogstra-Berends and Jouke-Jan Hottenga and Jensen, {Majken K.} and Asa Johansson and Juhani Junttila and Stefan Kaeaeb and Bart Kanon and Shamika Ketkar and Kay-Tee Khaw and Knowles, {Joshua W.} and Kooner, {Angrad S.} and Kors, {Jan A.} and Meena Kumari and Lili Milani and Paeivi Laiho and Lakatta, {Edward G.} and Claudia Langenberg and Maarten Leusink and Yongmei Liu and Luben, {Robert N.} and Lunetta, {Kathryn L.} and Lynch, {Stacey N.} and Markus, {Marcello R. P.} and Pedro Marques-Vidal and Leach, {Irene Mateo} and McArdle, {Wendy L.} and McCarroll, {Steven A.} and Medland, {Sarah E.} and Miller, {Kathryn A.} and Montgomery, {Grant W.} and Morrison, {Alanna C.} and Martina Mueller-Nurasyid and Pau Navarro and Mari Nelis and O'Connell, {Jeffrey R.} and O'Donnell, {Christopher J.} and Ong, {Ken K.} and Newman, {Anne B.} and Annette Peters and Ozren Polasek and Anneli Pouta and Pramstaller, {Peter P.} and Psaty, {Bruce M.} and Rao, {Dabeeru C.} and Ring, {Susan M.} and Rossin, {Elizabeth J.} and Diana Rudan and Serena Sanna and Scott, {Robert A.} and Sehmi, {Jaban S.} and Stephen Sharp and Shin, {Jordan T.} and Singleton, {Andrew B.} and Smith, {Albert V.} and Nicole Soranzo and Spector, {Tim D.} and Chip Stewart and Stringham, {Heather M.} and Tarasov, {Kirill V.} and Uitterlinden, {Andre G.} and Liesbeth Vandenput and Shih-Jen Hwang and Whitfield, {John B.} and Cisca Wijmenga and Wild, {Sarah H.} and Gonneke Willemsen and Wilson, {James F.} and Witteman, {Jacqueline C. M.} and Andrew Wong and Quenna Wong and Yalda Jamshidi and Paavo Zitting and Boer, {Jolanda M. A.} and Boomsma, {Dorret I.} and Borecki, {Ingrid B.} and {van Duijn}, {Cornelia M.} and Ulf Ekelund and Forouhi, {Nita G.} and Philippe Froguel and Aroon Hingorani and Erik Ingelsson and Mika Kivimaki and Kronmal, {Richard A.} and Diana Kuh and Lars Lind and Martin, {Nicholas G.} and Oostra, {Ben A.} and Pedersen, {Nancy L.} and Thomas Quertermous and Rotter, {Jerome I.} and {van der Schouw}, {Yvonne T.} and Verschuren, {W. M. Monique} and Mark Walker and Demetrius Albanes and Arnar, {David O.} and Assimes, {Themistocles L.} and Stefania Bandinelli and Michael Boehnke and {de Boer}, {Rudolf A.} and Claude Bouchard and Caulfield, {W. L. Mark} and Chambers, {John C.} and Gary Curhan and Daniele Cusi and Johan Eriksson and Luigi Ferrucci and {van Gilst}, {Wiek H.} and Nicola Glorioso and {de Graaf}, Jacqueline and Leif Groop and Ulf Gyllensten and Wen-Chi Hsueh and Hu, {Frank B.} and Huikuri, {Heikki V.} and Hunter, {David J.} and Carlos Iribarren and Bo Isomaa and Marjo-Riitta Jarvelin and Antti Jula and Mika Kahonen and Kiemeney, {Lambertus A.} and {van der Klauw}, {Melanie M.} and Kooner, {Jaspal S.} and Peter Kraft and Licia Iacoviello and Terho Lehtimaki and Lokki, {Marja-Liisa L.} and Mitchell, {Braxton D.} and Gerjan Navis and Nieminen, {Markku S.} and Claes Ohlsson and Poulter, {Neil R.} and Lu Qi and Raitakari, {Olli T.} and Rimm, {Eric B.} and Rioux, {John D.} and Federica Rizzi and Igor Rudan and Veikko Salomaa and Sever, {Peter S.} and Shields, {Denis C.} and Shuldiner, {Alan R.} and Juha Sinisalo and Stanton, {Alice V.} and Stolk, {Ronald P.} and Strachan, {David P.} and Jean-Claude Tardif and Unnur Thorsteinsdottir and Jaako Tuomilehto and {van Veldhuisen}, {Dirk J.} and Jarmo Virtamo and Jorma Viikari and Peter Vollenweider and Gerard Waeber and Elisabeth Widen and Cho, {Yoon Shin} and Olsen, {Jesper V.} and Visscher, {Peter M.} and Cristen Willer and Lude Franke and Jeanette Erdmann and Thompson, {John R.} and Arne Pfeufer and Nona Sotoodehnia and Christopher Newton-Cheh and Ellinor, {Patrick T.} and Stricker, {Bruno H. Ch} and Andres Metspalu and Markus Perola and Beckmann, {Jacques S.} and Smith, {George Davey} and Kari Stefansson and Wareham, {Nicholas J.} and Munroe, {Patricia B.} and Sibon, {Ody C. M.} and Milan, {David J.} and Harold Snieder and Samani, {Nilesh J.} and Loos, {Ruth J. F.}",
year = "2013",
doi = "10.1038/ng.2610",
language = "English",
volume = "45",
pages = "621--631",
journal = "Nature Genetics",
issn = "1546-1718",
publisher = "Nature Publishing Group",
number = "6",