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

Publication Type:

Journal Article

Authors:

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; Ardissino, Diego; 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; Mannucci, Pier M; Schwartz, Stephen M; Siscovick, David S; Yee, Jean; Friedlander, Yechiel; Elosua, Roberto; Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Sala, Joan; Ramos, Rafael; Kathiresan, Sekar; Meigs, James B; Williams, Gordon; Nathan, David M; MacRae, Calum A; O'Donnell, Christopher J; Salomaa, Veikko; Havulinna, Aki S; Peltonen, Leena; Melander, Olle; Berglund, Goran; Voight, Benjamin F; Kathiresan, Sekar; Hirschhorn, Joel N; Asselta, Rosanna; Duga, Stefano; Spreafico, Marta; Musunuru, Kiran; Daly, Mark J; Purcell, Shaun; Voight, Benjamin F; Purcell, Shaun; Nemesh, James; Korn, Joshua M; McCarroll, Steven A; Schwartz, Stephen M; Yee, Jean; Kathiresan, Sekar; Lucas, Gavin; Subirana, Isaac; Elosua, Roberto; Surti, Aarti; Guiducci, Candace; Gianniny, Lauren; Mirel, Daniel; Parkin, Melissa; Burtt, Noel; Gabriel, Stacey B; Samani, Nilesh J; Thompson, John R; Braund, Peter S; Wright, Benjamin J; Balmforth, Anthony J; Ball, Stephen G; Hall, Alistair S; Schunkert, Heribert; Erdmann, Jeanette; Linsel-Nitschke, Patrick; Lieb, Wolfgang; Ziegler, Andreas; König, Inke; Hengstenberg, Christian; Fischer, Marcus; Stark, Klaus; Grosshennig, Anika; Preuss, Michael; Wichmann, H-Erich; Schreiber, Stefan; Schunkert, Heribert; Samani, Nilesh J; Erdmann, Jeanette; Ouwehand, Willem; Hengstenberg, Christian; Deloukas, Panos; Scholz, Michael; Cambien, Francois; Reilly, Muredach P; 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; Rader, Daniel J; Scheffold, Thomas; Berger, Klaus; Stoll, Monika; Huge, Andreas; Girelli, Domenico; Martinelli, Nicola; Olivieri, Oliviero; Corrocher, Roberto; Morgan, Thomas; Spertus, John A; McKeown, Pascal; Patterson, Chris C; Schunkert, Heribert; Erdmann, Erdmann; Linsel-Nitschke, Patrick; Lieb, Wolfgang; Ziegler, Andreas; König, Inke R; Hengstenberg, Christian; Fischer, Marcus; Stark, Klaus; Grosshennig, Anika; Preuss, Michael; Wichmann, H-Erich; Schreiber, Stefan; Hólm, Hilma; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Engert, James C; Do, Ron; Xie, Changchun; Anand, Sonia; Kathiresan, Sekar; Ardissino, Diego; Mannucci, Pier M; Siscovick, David; O'Donnell, Christopher J; Samani, Nilesh J; Melander, Olle; Elosua, Roberto; Peltonen, Leena; Salomaa, Veikko; Schwartz, Stephen M; Altshuler, David

Source:

Nature genetics, Volume 41, Issue 3, p.334-41 (2009)

Keywords:

2009, Adult, Age of Onset, Algorithms, Case-Control Studies, Center-Authored Paper, Female, Gene Dosage, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Mutation, Myocardial Infarction, Polymorphism, Single Nucleotide, Public Health Sciences Division, Risk Factors

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.