title: Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction.
abstract: Sudden cardiac death from ventricular fibrillation during acute myocardial infarction is a leading cause of total and cardiovascular mortality. To our knowledge, we here report the first genome-wide association study for this trait, conducted in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillation was found at 21q21 (rs2824292, odds ratio = 1.78, 95% CI 1.47-2.13, P = 3.3 x 10(-10)). The association of rs2824292 with ventricular fibrillation was replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest individuals with myocardial infarction complicated by ventricular fibrillation and 391 individuals who survived a myocardial infarction (controls) (odds ratio = 1.49, 95% CI 1.14-1.95, P = 0.004). The closest gene to this SNP is CXADR, which encodes a viral receptor previously implicated in myocarditis and dilated cardiomyopathy and which has recently been identified as a modulator of cardiac conduction. This locus has not previously been implicated in arrhythmia susceptibility.
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Connie R
authors.initials: CR
authors.lastname: Bezzina
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Raha
authors.initials: R
authors.lastname: Pazoki
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Abdennasser
authors.initials: A
authors.lastname: Bardai
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Roos F
authors.initials: RF
authors.lastname: Marsman
authors.affiliation: Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jonas S S G
authors.initials: JSSG
authors.lastname: de Jong
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marieke T
authors.initials: MT
authors.lastname: Blom
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Brendon P
authors.initials: BP
authors.lastname: Scicluna
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.|Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.affiliation: Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Social Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Navin R
authors.initials: NR
authors.lastname: Bindraban
authors.affiliation: Institute of Human Genetics, Klinikum Rechts der Isar Technische Universität München, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.affiliation: Institute of Human Genetics, Klinikum Rechts der Isar Technische Universität München, Munich, Germany.|Institute of Human Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Pfeufer
authors.affiliation: Division of Cardiology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.|Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA.|Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Nanette H
authors.initials: NH
authors.lastname: Bishopric
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Institute of Human Genetics, Klinikum Rechts der Isar Technische Universität München, Munich, Germany.|Institute of Human Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.affiliation: The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Sumeet S
authors.initials: SS
authors.lastname: Chugh
authors.affiliation: Division of Cardiology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Myerburg
authors.affiliation: Université Paris Descartes, Assistance Publique-Hopitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jouven
authors.affiliation: Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kääb
authors.affiliation: Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: Lukas R C
authors.initials: LRC
authors.lastname: Dekker
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michael W T
authors.initials: MWT
authors.lastname: Tanck
authors.affiliation: Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Arthur A M
authors.initials: AAM
authors.lastname: Wilde
mesh_terms: D000208:Acute Disease; D000368:Aged; D056988:Anterior Wall Myocardial Infarction; D001145:Arrhythmias, Cardiac / Q000150:complications; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004198:Disease Susceptibility / Q000150:complications; D005260:Female; D055106:Genome-Wide Association Study; D006323:Heart Arrest / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D009426:Netherlands; D016017:Odds Ratio; D014693:Ventricular Fibrillation / Q000150:complications* / Q000401:mortality* / Q000503:physiopathology