Evidence map›Paper›PMID 23583979›Full record

SynthesisNature genetics2013

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

Marcel den Hoed, Mark Eijgelsheim, Tõnu Esko, Bianca J J M Brundel, David S Peal, David M Evans, Ilja M Nolte, Ayellet V Segrè, Hilma Holm, Robert E Handsaker and 264 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed, 16 pooled it
17.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

171 citing papers in PubMed, 16 syntheses or guidelines pooled it, 319 citations in OpenAlex.

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  17. βJournal of clinical pharmacology · 2019
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111 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

274 authors at 20 institutions in 21 countries.

Marcel den HoedMedical Research Council MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Mark Eijgelsheim
Tõnu Esko
Bianca J J M Brundel
David S Peal
David M Evans
Ilja M Nolte
Ayellet V Segrè
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
Zoltán 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
Søren Brage
Stephen J Chanock
Peter S Chines
Mina Chung
Dawood Darbar
Christian Dina
Marcus Dörr
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 Kääb
Bart Kanon
Shamika Ketkar
Kay-Tee Khaw
Joshua W Knowles
Angrad S Kooner
Jan A Kors
Meena Kumari
Lili Milani
Päivi 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 Müller-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
André 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 Kähönen
Lambertus A Kiemeney
Melanie M van der Klauw
Jaspal S Kooner
Peter Kraft
Licia Iacoviello
Terho Lehtimäki
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
Gérard Waeber
Elisabeth Widen
Yoon Shin Cho
Jesper V Olsen
Peter M Visscher
Cristen Willer
Lude Franke
Global BPgen Consortium
CARDIoGRAM Consortium
Jeanette Erdmann
John R Thompson
PR GWAS Consortium
Arne Pfeufer
QRS GWAS Consortium
Nona Sotoodehnia
QT-IGC Consortium
Christopher Newton-Cheh
CHARGE-AF Consortium
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
University Medical Center Groningen · NLAddenbrooke's Hospital · GBHarvard University · USBroad Institute · USUniversity of Bristol · GBUniversity of Washington · USErasmus MC · NLImperial College London · GBMassachusetts General Hospital · USNational Institute on Aging · USAmsterdam Public Health · NLFinnish Institute for Health and Welfare · FIUniversity of Helsinki · FIUniversity of Michigan · USCentre National de la Recherche Scientifique · FRdeCODE Genetics (Iceland) · ISMontreal Heart Institute · CANational Health Service · GBQIMR Berghofer Medical Research Institute · AUQueen Mary University of London · GB

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLIAM H HERMAN · 2013 to 2026
$24.3M
Pharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Functional Genomics of Atrial Fibrillation in Human AtriaR01HL111314 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BARNARD, JOHN, CHUNG, MINA KAY · 2012 to 2019
$6.1M
The Aging Genome Association Study "AGE-GAIN"ZIAAG000965 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$4.0M
Genetics of Atrial FibrillationR01HL090620 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BARNARD, JOHN, CHUNG, MINA KAY · 2008 to 2012
$2.9M
Positional Cloning and Candidate Gene Approach to Familial Atrial FibrillationR01HL092217 · NHLBI · VANDERBILT UNIVERSITY · PI DARBAR, DAWOOD · 2009 to 2017
$2.9M
Genome-wide Association Study of Cardiovascular Traits in 6142 SardiniansZIAAG000799 · NIA · NATIONAL INSTITUTE ON AGING · PI LAKATTA, EDWARD · 2009 to 2025
$1.8M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
British Heart Foundation PG/12/38/29615Chief Scientist Office CZB/4/710Medical Research Council G0401527Medical Research Council G0600705Medical Research Council G0801056Medical Research Council G1000143Medical Research Council G1002084Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_U127561128Medical Research Council MC_PC_U127592696Medical Research Council MC_U106179471Medical Research Council MC_U106179472Medical Research Council MC_U106179473Medical Research Council MC_U106188470Medical Research Council MC_U123092720Medical Research Council MC_U127592696Medical Research Council MC_UP_A100_1003Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12013/4Medical Research Council MC_UU_12015/2NCATS NIH HHS UL1 TR000124NHLBI NIH HHS K24 HL105780NHLBI NIH HHS R00 HL094535NHLBI NIH HHS R01 HL090620NHLBI NIH HHS R01 HL092217NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL111314NHLBI NIH HHS U19 HL065962NIDA NIH HHS R21 DA026982NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK063491NIGMS NIH HHS T32 GM007753Wellcome Trust 092731
6 · The paper itself

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.

Indexed as

AnimalsArrhythmias, CardiacGene FrequencyGenetic LociGenome-Wide Association StudyHeart Conduction SystemHeart RateHumansMetabolic Networks and PathwaysPolymorphism, Single NucleotideQuantitative Trait Loci

Identifiers

PMID23583979
PMCPMC3696959
OpenAlexW1992911777

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.