Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23583979
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.
DATE PUBLISHED
2013 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/12/07
accepted 2013/03/21
aheadofprint 2013/04/14
entrez 2013/04/16 06:00
pubmed 2013/04/16 06:00
medline 2013/08/03 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
den Hoed M den Hoed Marcel M Medical Research Council MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Eijgelsheim M Eijgelsheim Mark M
Esko T Esko Tõnu T
Brundel BJ Brundel Bianca J J M BJ
Peal DS Peal David S DS
Evans DM Evans David M DM
Nolte IM Nolte Ilja M IM
Segrè AV Segrè Ayellet V AV
Holm H Holm Hilma H
Handsaker RE Handsaker Robert E RE
Westra HJ Westra Harm-Jan HJ
Johnson T Johnson Toby T
Isaacs A Isaacs Aaron A
Yang J Yang Jian J
Lundby A Lundby Alicia A
Zhao JH Zhao Jing Hua JH
Kim YJ Kim Young Jin YJ
Go MJ Go Min Jin MJ
Almgren P Almgren Peter P
Bochud M Bochud Murielle M
Boucher G Boucher Gabrielle G
Cornelis MC Cornelis Marilyn C MC
Gudbjartsson D Gudbjartsson Daniel D
Hadley D Hadley David D
van der Harst P van der Harst Pim P
Hayward C Hayward Caroline C
den Heijer M den Heijer Martin M
Igl W Igl Wilmar W
Jackson AU Jackson Anne U AU
Kutalik Z Kutalik Zoltán Z
Luan J Luan Jian'an J
Kemp JP Kemp John P JP
Kristiansson K Kristiansson Kati K
Ladenvall C Ladenvall Claes C
Lorentzon M Lorentzon Mattias M
Montasser ME Montasser May E ME
Njajou OT Njajou Omer T OT
O'Reilly PF O'Reilly Paul F PF
Padmanabhan S Padmanabhan Sandosh S
St Pourcain B St Pourcain Beate B
Rankinen T Rankinen Tuomo T
Salo P Salo Perttu P
Tanaka T Tanaka Toshiko T
Timpson NJ Timpson Nicholas J NJ
Vitart V Vitart Veronique V
Waite L Waite Lindsay L
Wheeler W Wheeler William W
Zhang W Zhang Weihua W
Draisma HH Draisma Harmen H M HH
Feitosa MF Feitosa Mary F MF
Kerr KF Kerr Kathleen F KF
Lind PA Lind Penelope A PA
Mihailov E Mihailov Evelin E
Onland-Moret NC Onland-Moret N Charlotte NC
Song C Song Ci C
Weedon MN Weedon Michael N MN
Xie W Xie Weijia W
Yengo L Yengo Loic L
Absher D Absher Devin D
Albert CM Albert Christine M CM
Alonso A Alonso Alvaro A
Arking DE Arking Dan E DE
de Bakker PI de Bakker Paul I W PI
Balkau B Balkau Beverley B
Barlassina C Barlassina Cristina C
Benaglio P Benaglio Paola P
Bis JC Bis Joshua C JC
Bouatia-Naji N Bouatia-Naji Nabila N
Brage S Brage Søren S
Chanock SJ Chanock Stephen J SJ
Chines PS Chines Peter S PS
Chung M Chung Mina M
Darbar D Darbar Dawood D
Dina C Dina Christian C
Dörr M Dörr Marcus M
Elliott P Elliott Paul P
Felix SB Felix Stephan B SB
Fischer K Fischer Krista K
Fuchsberger C Fuchsberger Christian C
de Geus EJ de Geus Eco J C EJ
Goyette P Goyette Philippe P
Gudnason V Gudnason Vilmundur V
Harris TB Harris Tamara B TB
Hartikainen AL Hartikainen Anna-Liisa AL
Havulinna AS Havulinna Aki S AS
Heckbert SR Heckbert Susan R SR
Hicks AA Hicks Andrew A AA
Hofman A Hofman Albert A
Holewijn S Holewijn Suzanne S
Hoogstra-Berends F Hoogstra-Berends Femke F
Hottenga JJ Hottenga Jouke-Jan JJ
Jensen MK Jensen Majken K MK
Johansson A Johansson Asa A
Junttila J Junttila Juhani J
Kääb S Kääb Stefan S
Kanon B Kanon Bart B
Ketkar S Ketkar Shamika S
Khaw KT Khaw Kay-Tee KT
Knowles JW Knowles Joshua W JW
Kooner AS Kooner Angrad S AS
Kors JA Kors Jan A JA
Kumari M Kumari Meena M
Milani L Milani Lili L
Laiho P Laiho Päivi P
Lakatta EG Lakatta Edward G EG
Langenberg C Langenberg Claudia C
Leusink M Leusink Maarten M
Liu Y Liu Yongmei Y
Luben RN Luben Robert N RN
Lunetta KL Lunetta Kathryn L KL
Lynch SN Lynch Stacey N SN
Markus MR Markus Marcello R P MR
Marques-Vidal P Marques-Vidal Pedro P
Mateo Leach I Mateo Leach Irene I
McArdle WL McArdle Wendy L WL
McCarroll SA McCarroll Steven A SA
Medland SE Medland Sarah E SE
Miller KA Miller Kathryn A KA
Montgomery GW Montgomery Grant W GW
Morrison AC Morrison Alanna C AC
Müller-Nurasyid M Müller-Nurasyid Martina M
Navarro P Navarro Pau P
Nelis M Nelis Mari M
O'Connell JR O'Connell Jeffrey R JR
O'Donnell CJ O'Donnell Christopher J CJ
Ong KK Ong Ken K KK
Newman AB Newman Anne B AB
Peters A Peters Annette A
Polasek O Polasek Ozren O
Pouta A Pouta Anneli A
Pramstaller PP Pramstaller Peter P PP
Psaty BM Psaty Bruce M BM
Rao DC Rao Dabeeru C DC
Ring SM Ring Susan M SM
Rossin EJ Rossin Elizabeth J EJ
Rudan D Rudan Diana D
Sanna S Sanna Serena S
Scott RA Scott Robert A RA
Sehmi JS Sehmi Jaban S JS
Sharp S Sharp Stephen S
Shin JT Shin Jordan T JT
Singleton AB Singleton Andrew B AB
Smith AV Smith Albert V AV
Soranzo N Soranzo Nicole N
Spector TD Spector Tim D TD
Stewart C Stewart Chip C
Stringham HM Stringham Heather M HM
Tarasov KV Tarasov Kirill V KV
Uitterlinden AG Uitterlinden André G AG
Vandenput L Vandenput Liesbeth L
Hwang SJ Hwang Shih-Jen SJ
Whitfield JB Whitfield John B JB
Wijmenga C Wijmenga Cisca C
Wild SH Wild Sarah H SH
Willemsen G Willemsen Gonneke G
Wilson JF Wilson James F JF
Witteman JC Witteman Jacqueline C M JC
Wong A Wong Andrew A
Wong Q Wong Quenna Q
Jamshidi Y Jamshidi Yalda Y
Zitting P Zitting Paavo P
Boer JM Boer Jolanda M A JM
Boomsma DI Boomsma Dorret I DI
Borecki IB Borecki Ingrid B IB
van Duijn CM van Duijn Cornelia M CM
Ekelund U Ekelund Ulf U
Forouhi NG Forouhi Nita G NG
Froguel P Froguel Philippe P
Hingorani A Hingorani Aroon A
Ingelsson E Ingelsson Erik E
Kivimaki M Kivimaki Mika M
Kronmal RA Kronmal Richard A RA
Kuh D Kuh Diana D
Lind L Lind Lars L
Martin NG Martin Nicholas G NG
Oostra BA Oostra Ben A BA
Pedersen NL Pedersen Nancy L NL
Quertermous T Quertermous Thomas T
Rotter JI Rotter Jerome I JI
van der Schouw YT van der Schouw Yvonne T YT
Verschuren WM Verschuren W M Monique WM
Walker M Walker Mark M
Albanes D Albanes Demetrius D
Arnar DO Arnar David O DO
Assimes TL Assimes Themistocles L TL
Bandinelli S Bandinelli Stefania S
Boehnke M Boehnke Michael M
de Boer RA de Boer Rudolf A RA
Bouchard C Bouchard Claude C
Caulfield WL Caulfield W L Mark WL
Chambers JC Chambers John C JC
Curhan G Curhan Gary G
Cusi D Cusi Daniele D
Eriksson J Eriksson Johan J
Ferrucci L Ferrucci Luigi L
van Gilst WH van Gilst Wiek H WH
Glorioso N Glorioso Nicola N
de Graaf J de Graaf Jacqueline J
Groop L Groop Leif L
Gyllensten U Gyllensten Ulf U
Hsueh WC Hsueh Wen-Chi WC
Hu FB Hu Frank B FB
Huikuri HV Huikuri Heikki V HV
Hunter DJ Hunter David J DJ
Iribarren C Iribarren Carlos C
Isomaa B Isomaa Bo B
Jarvelin MR Jarvelin Marjo-Riitta MR
Jula A Jula Antti A
Kähönen M Kähönen Mika M
Kiemeney LA Kiemeney Lambertus A LA
van der Klauw MM van der Klauw Melanie M MM
Kooner JS Kooner Jaspal S JS
Kraft P Kraft Peter P
Iacoviello L Iacoviello Licia L
Lehtimäki T Lehtimäki Terho T
Lokki ML Lokki Marja-Liisa L ML
Mitchell BD Mitchell Braxton D BD
Navis G Navis Gerjan G
Nieminen MS Nieminen Markku S MS
Ohlsson C Ohlsson Claes C
Poulter NR Poulter Neil R NR
Qi L Qi Lu L
Raitakari OT Raitakari Olli T OT
Rimm EB Rimm Eric B EB
Rioux JD Rioux John D JD
Rizzi F Rizzi Federica F
Rudan I Rudan Igor I
Salomaa V Salomaa Veikko V
Sever PS Sever Peter S PS
Shields DC Shields Denis C DC
Shuldiner AR Shuldiner Alan R AR
Sinisalo J Sinisalo Juha J
Stanton AV Stanton Alice V AV
Stolk RP Stolk Ronald P RP
Strachan DP Strachan David P DP
Tardif JC Tardif Jean-Claude JC
Thorsteinsdottir U Thorsteinsdottir Unnur U
Tuomilehto J Tuomilehto Jaako J
van Veldhuisen DJ van Veldhuisen Dirk J DJ
Virtamo J Virtamo Jarmo J
Viikari J Viikari Jorma J
Vollenweider P Vollenweider Peter P
Waeber G Waeber Gérard G
Widen E Widen Elisabeth E
Cho YS Cho Yoon Shin YS
Olsen JV Olsen Jesper V JV
Visscher PM Visscher Peter M PM
Willer C Willer Cristen C
Franke L Franke Lude L
Global BPgen Consortium
CARDIoGRAM Consortium
Erdmann J Erdmann Jeanette J
Thompson JR Thompson John R JR
PR GWAS Consortium
Pfeufer A Pfeufer Arne A
QRS GWAS Consortium
Sotoodehnia N Sotoodehnia Nona N
QT-IGC Consortium
Newton-Cheh C Newton-Cheh Christopher C
CHARGE-AF Consortium
Ellinor PT Ellinor Patrick T PT
Stricker BH Stricker Bruno H Ch BH
Metspalu A Metspalu Andres A
Perola M Perola Markus M
Beckmann JS Beckmann Jacques S JS
Smith GD Smith George Davey GD
Stefansson K Stefansson Kari K
Wareham NJ Wareham Nicholas J NJ
Munroe PB Munroe Patricia B PB
Sibon OC Sibon Ody C M OC
Milan DJ Milan David J DJ
Snieder H Snieder Harold H
Samani NJ Samani Nilesh J NJ
Loos RJ Loos Ruth J F RJ
INVESTIGATORS
JOURNAL
VOLUME: 45
ISSUE: 6
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2013
MONTH: Jun
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
092731 Wellcome Trust United Kingdom
CZB/4/710 Chief Scientist Office United Kingdom
G0600705 Medical Research Council United Kingdom
G0801056 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
G1002084 Medical Research Council United Kingdom
G9815508 Medical Research Council United Kingdom
K24 HL105780 NHLBI NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
MC_PC_U127561128 Medical Research Council United Kingdom
MC_U106179471 Medical Research Council United Kingdom
MC_U106179472 Medical Research Council United Kingdom
MC_U106179473 Medical Research Council United Kingdom
MC_U106188470 Medical Research Council United Kingdom
MC_U123092720 Medical Research Council United Kingdom
MC_U127592696 Medical Research Council United Kingdom
MC_UP_A100_1003 Medical Research Council United Kingdom
MC_UU_12013/1 Medical Research Council United Kingdom
MC_UU_12013/3 Medical Research Council United Kingdom
P30 DK063491 NIDDK NIH HHS United States
PG/12/38/29615 British Heart Foundation United Kingdom
R00 HL094535 NHLBI NIH HHS United States
R01 HL090620 NHLBI NIH HHS United States
R01 HL092217 NHLBI NIH HHS United States
R01 HL105756 NHLBI NIH HHS United States
R01 HL111314 NHLBI NIH HHS United States
R21 DA026982 NIDA NIH HHS United States
T32 GM007753 NIGMS NIH HHS United States
U19 HL065962 NHLBI NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Animals
Arrhythmias, Cardiac physiopathology
Gene Frequency physiopathology
Genetic Loci physiopathology
Genome-Wide Association Study physiopathology
Heart Conduction System physiopathology
Heart Rate genetics
Humans genetics
Metabolic Networks and Pathways genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS473857 NLM
PMC3696959 NLM