Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
Författare
- Marcel den Hoed
- Mark Eijgelsheim
- Tonu Esko
- Bianca J. J. M. Brundel
- David S. Peal
- David M. Evans
- Ilja M. Nolte
- Ayellet V. Segre
- Hilma Holm
- Robert E. Handsaker
- Harm-Jan Westra
- Toby Johnson
- Aaron Isaacs
- Jian Yang
- Alicia Lundby
- Jing Hua Zhao
- Young Jin Kim
- Min Jin Go
- Peter Almgren
- Murielle Bochud
- Gabrielle Boucher
- Marilyn C. Cornelis
- Daniel Gudbjartsson
- David Hadley
- Pim van der Harst
- Caroline Hayward
- Martin den Heijer
- Wilmar Igl
- Anne U. Jackson
- Zoltan Kutalik
- Jian'an Luan
- John P. Kemp
- Kati Kristiansson
- Claes Ladenvall
- Mattias Lorentzon
- May E. Montasser
- Omer T. Njajou
- Paul F. O'Reilly
- Sandosh Padmanabhan
- Beate St. Pourcain
- Tuomo Rankinen
- Perttu Salo
- Toshiko Tanaka
- Nicholas J. Timpson
- Veronique Vitart
- Lindsay Waite
- William Wheeler
- Weihua Zhang
- Harmen H. M. Draisma
- Mary F. Feitosa
- Kathleen F. Kerr
- Penelope A. Lind
- Evelin Mihailov
- N. Charlotte Onland-Moret
- Ci Song
- Michael N. Weedon
- Weijia Xie
- Loic Yengo
- Devin Absher
- Christine M. Albert
- Alvaro Alonso
- Dan E. Arking
- Paul I. W. de Bakker
- Beverley Balkau
- Cristina Barlassina
- Paola Benaglio
- Joshua C. Bis
- Nabila Bouatia-Naji
- Soren Brage
- Stephen J. Chanock
- Peter S. Chines
- Mina Chung
- Dawood Darbar
- Christian Dina
- Marcus Doerr
- Paul Elliott
- Stephan B. Felix
- Krista Fischer
- Christian Fuchsberger
- Eco J. C. de Geus
- Philippe Goyette
- Vilmundur Gudnason
- Tamara B. Harris
- Anna-Liisa Hartikainen
- Aki S. Havulinna
- Susan R. Heckbert
- Andrew A. Hicks
- Albert Hofman
- Suzanne Holewijn
- Femke Hoogstra-Berends
- Jouke-Jan Hottenga
- Majken K. Jensen
- Asa Johansson
- Juhani Junttila
- Stefan Kaeaeb
- Bart Kanon
- Shamika Ketkar
- Kay-Tee Khaw
- Joshua W. Knowles
- Angrad S. Kooner
- Jan A. Kors
- Meena Kumari
- Lili Milani
- Paeivi Laiho
- Edward G. Lakatta
- Claudia Langenberg
- Maarten Leusink
- Yongmei Liu
- Robert N. Luben
- Kathryn L. Lunetta
- Stacey N. Lynch
- Marcello R. P. Markus
- Pedro Marques-Vidal
- Irene Mateo Leach
- Wendy L. McArdle
- Steven A. McCarroll
- Sarah E. Medland
- Kathryn A. Miller
- Grant W. Montgomery
- Alanna C. Morrison
- Martina Mueller-Nurasyid
- Pau Navarro
- Mari Nelis
- Jeffrey R. O'Connell
- Christopher J. O'Donnell
- Ken K. Ong
- Anne B. Newman
- Annette Peters
- Ozren Polasek
- Anneli Pouta
- Peter P. Pramstaller
- Bruce M. Psaty
- Dabeeru C. Rao
- Susan M. Ring
- Elizabeth J. Rossin
- Diana Rudan
- Serena Sanna
- Robert A. Scott
- Jaban S. Sehmi
- Stephen Sharp
- Jordan T. Shin
- Andrew B. Singleton
- Albert V. Smith
- Nicole Soranzo
- Tim D. Spector
- Chip Stewart
- Heather M. Stringham
- Kirill V. Tarasov
- Andre G. Uitterlinden
- Liesbeth Vandenput
- Shih-Jen Hwang
- John B. Whitfield
- Cisca Wijmenga
- Sarah H. Wild
- Gonneke Willemsen
- James F. Wilson
- Jacqueline C. M. Witteman
- Andrew Wong
- Quenna Wong
- Yalda Jamshidi
- Paavo Zitting
- Jolanda M. A. Boer
- Dorret I. Boomsma
- Ingrid B. Borecki
- Cornelia M. van Duijn
- Ulf Ekelund
- Nita G. Forouhi
- Philippe Froguel
- Aroon Hingorani
- Erik Ingelsson
- Mika Kivimaki
- Richard A. Kronmal
- Diana Kuh
- Lars Lind
- Nicholas G. Martin
- Ben A. Oostra
- Nancy L. Pedersen
- Thomas Quertermous
- Jerome I. Rotter
- Yvonne T. van der Schouw
- W. M. Monique Verschuren
- Mark Walker
- Demetrius Albanes
- David O. Arnar
- Themistocles L. Assimes
- Stefania Bandinelli
- Michael Boehnke
- Rudolf A. de Boer
- Claude Bouchard
- W. L. Mark Caulfield
- John C. Chambers
- Gary Curhan
- Daniele Cusi
- Johan Eriksson
- Luigi Ferrucci
- Wiek H. van Gilst
- Nicola Glorioso
- Jacqueline de Graaf
- Leif Groop
- Ulf Gyllensten
- Wen-Chi Hsueh
- Frank B. Hu
- Heikki V. Huikuri
- David J. Hunter
- Carlos Iribarren
- Bo Isomaa
- Marjo-Riitta Jarvelin
- Antti Jula
- Mika Kahonen
- Lambertus A. Kiemeney
- Melanie M. van der Klauw
- Jaspal S. Kooner
- Peter Kraft
- Licia Iacoviello
- Terho Lehtimaki
- Marja-Liisa L. Lokki
- Braxton D. Mitchell
- Gerjan Navis
- Markku S. Nieminen
- Claes Ohlsson
- Neil R. Poulter
- Lu Qi
- Olli T. Raitakari
- Eric B. Rimm
- John D. Rioux
- Federica Rizzi
- Igor Rudan
- Veikko Salomaa
- Peter S. Sever
- Denis C. Shields
- Alan R. Shuldiner
- Juha Sinisalo
- Alice V. Stanton
- Ronald P. Stolk
- David P. Strachan
- Jean-Claude Tardif
- Unnur Thorsteinsdottir
- Jaako Tuomilehto
- Dirk J. van Veldhuisen
- Jarmo Virtamo
- Jorma Viikari
- Peter Vollenweider
- Gerard Waeber
- Elisabeth Widen
- Yoon Shin Cho
- Jesper V. Olsen
- Peter M. Visscher
- Cristen Willer
- Lude Franke
- Jeanette Erdmann
- John R. Thompson
- Arne Pfeufer
- Nona Sotoodehnia
- Christopher Newton-Cheh
- Patrick T. Ellinor
- Bruno H. Ch Stricker
- Andres Metspalu
- Markus Perola
- Jacques S. Beckmann
- George Davey Smith
- Kari Stefansson
- Nicholas J. Wareham
- Patricia B. Munroe
- Ody C. M. Sibon
- David J. Milan
- Harold Snieder
- Nilesh J. Samani
- Ruth J. F. Loos
Summary, in English
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.
Publiceringsår
2013
Språk
Engelska
Sidor
621-631
Publikation/Tidskrift/Serie
Nature Genetics
Volym
45
Issue
6
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Endocrinology and Diabetes
Status
Published
Forskningsgrupp
- Translational Muscle Research
ISBN/ISSN/Övrigt
- ISSN: 1546-1718