Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

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

Research output: Contribution to journalArticlepeer-review

949 Scopus citations


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 observations1-4 (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.

Original languageEnglish
Pages (from-to)334-341
Number of pages8
JournalNature Genetics
Issue number3
StatePublished - Mar 2009
Externally publishedYes


Dive into the research topics of 'Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants'. Together they form a unique fingerprint.

Cite this