Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction

Connie R. Bezzina, Raha Pazoki, Abdennasser Bardai, Roos F. Marsman, Jonas S.S.G. De Jong, Marieke T. Blom, Brendon P. Scicluna, J. Wouter Jukema, Navin R. Bindraban, Peter Lichtner, Arne Pfeufer, Nanette H. Bishopric, Dan M. Roden, Thomas Meitinger, Sumeet S. Chugh, Robert J. Myerburg, Xavier Jouven, Stefan Kääb, Lukas R.C. Dekker, Hanno L. TanMichael W.T. Tanck, Arthur A.M. Wilde

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

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 × 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.

Original languageEnglish (US)
Pages (from-to)688-691
Number of pages4
JournalNature genetics
Volume42
Issue number8
DOIs
StatePublished - Aug 2010

ASJC Scopus subject areas

  • Genetics

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