Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants by Myocardial Infarction Genetics Consortium, Kathiresan Sekar, Voight Benjamin F, Purcell Shaun, Musunuru Kiran, Ardissino Diego, Mannucci Pier M, Anand Sonia, Engert James C, Samani Nilesh J, Schunkert Heribert, Erdmann Jeanette, Reilly Muredach P, Rader Daniel J, Morgan Thomas, Spertus John A, Stoll Monika, Girelli Domenico, McKeown Pascal P, Patterson Chris C, Siscovick David S, O'Donnell Christopher J, Elosua Roberto, Peltonen Leena, Salomaa Veikko, Schwartz Stephen M, Melander Olle, Altshuler David, Merlini Pier Angelica, Berzuini Carlo, Bernardinelli Luisa, Peyvandi Flora, Tubaro Marco, Celli Patrizia, Ferrario Maurizio, Fetiveau Raffaela, Marziliano Nicola, Casari Giorgio, Galli Michele, Ribichini Flavio, Rossi Marco, Bernardi Francesco, Zonzin Pietro, Piazza Alberto, Yee Jean, Friedlander Yechiel, Marrugat Jaume, Lucas Gavin, Subirana Isaac, Sala Joan, Ramos Rafael, Meigs James B, Williams Gordon, Nathan David M, MacRae Calum A, Havulinna Aki S, Berglund Goran, Hirschhorn Joel N, Asselta Rosanna, Duga Stefano, Spreafico Marta, Daly Mark J, Nemesh James, Korn Joshua M, McCarroll Steven A, Surti Aarti, Guiducci Candace, Gianniny Lauren, Mirel Daniel, Parkin Melissa, Burtt Noel, Gabriel Stacey B, Thompson John R, Braund Peter S, Wright Benjamin J, Balmforth Anthony J, Ball Stephen G, Hall Alistair S, Wellcome Trust Case Control Consortium, Linsel-Nitschke Patrick, Lieb Wolfgang, Ziegler Andreas, König Inke, Hengstenberg Christian, Fischer Marcus, Stark Klaus, Grosshennig Anika, Preuss Michael, Wichmann H-Erich, Schreiber Stefan, Ouwehand Willem, Deloukas Panos, Scholz Michael, Cambien Francois, Li Mingyao, Chen Zhen, Wilensky Robert, Matthai William, Qasim Atif, Hakonarson Hakon H, Devaney Joe, Burnett Mary-Susan, Pichard Augusto D, Kent Kenneth M, Satler Lowell, Lindsay Joseph M, Waksman Ron, Knouff Christopher W, Waterworth Dawn M, Walker Max C, Mooser Vincent, Epstein Stephen E, Scheffold Thomas, Berger Klaus, Huge Andreas, Martinelli Nicola, Olivieri Oliviero, Corrocher Roberto, McKeown Pascal, Erdmann Erdmann, König Inke R, Hólm Hilma, Thorleifsson Gudmar, Thorsteinsdottir Unnur, Stefansson Kari, Do Ron, Xie Changchun, Siscovick David in Nature genetics (2009). PubMed

Abstract

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10(-3)). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

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