Document Detail


Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.
MedLine Citation:
PMID:  19198609     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
; 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 Siscovick; Christopher J O'Donnell; Roberto Elosua; Leena Peltonen; Veikko Salomaa; Stephen M Schwartz; Olle Melander; David Altshuler; Diego Ardissino; 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; Pier M Mannucci; Stephen M Schwartz; David S Siscovick; Jean Yee; Yechiel Friedlander; Roberto Elosua; Jaume Marrugat; Gavin Lucas; Isaac Subirana; Joan Sala; Rafael Ramos; Sekar Kathiresan; James B Meigs; Gordon Williams; David M Nathan; Calum A MacRae; Christopher J O'Donnell; Veikko Salomaa; Aki S Havulinna; Leena Peltonen; Olle Melander; Goran Berglund; Benjamin F Voight; Sekar Kathiresan; Joel N Hirschhorn; Rosanna Asselta; Stefano Duga; Marta Spreafico; Kiran Musunuru; Mark J Daly; Shaun Purcell; Benjamin F Voight; Shaun Purcell; James Nemesh; Joshua M Korn; Steven A McCarroll; Stephen M Schwartz; Jean Yee; Sekar Kathiresan; Gavin Lucas; Isaac Subirana; Roberto Elosua; Aarti Surti; Candace Guiducci; Lauren Gianniny; Daniel Mirel; Melissa Parkin; Noel Burtt; Stacey B Gabriel; Nilesh J Samani; John R Thompson; Peter S Braund; Benjamin J Wright; Anthony J Balmforth; Stephen G Ball; Alistair S Hall; ; Heribert Schunkert; Jeanette Erdmann; Patrick Linsel-Nitschke; Wolfgang Lieb; Andreas Ziegler; Inke König; Christian Hengstenberg; Marcus Fischer; Klaus Stark; Anika Grosshennig; Michael Preuss; H-Erich Wichmann; Stefan Schreiber; Heribert Schunkert; Nilesh J Samani; Jeanette Erdmann; Willem Ouwehand; Christian Hengstenberg; Panos Deloukas; Michael Scholz; Francois Cambien; Muredach P Reilly; 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; Christopher W Knouff; Dawn M Waterworth; Max C Walker; Vincent Mooser; Stephen E Epstein; Daniel J Rader; Thomas Scheffold; Klaus Berger; Monika Stoll; Andreas Huge; Domenico Girelli; Nicola Martinelli; Oliviero Olivieri; Roberto Corrocher; Thomas Morgan; John A Spertus; Pascal McKeown; Chris C Patterson; Heribert Schunkert; Erdmann Erdmann; 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; Hilma Hólm; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Kari Stefansson; James C Engert; Ron Do; Changchun Xie; Sonia Anand; Sekar Kathiresan; Diego Ardissino; Pier M Mannucci; David Siscovick; Christopher J O'Donnell; Nilesh J Samani; Olle Melander; Roberto Elosua; Leena Peltonen; Veikko Salomaa; Stephen M Schwartz; David Altshuler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-02-08
Journal Detail:
Title:  Nature genetics     Volume:  41     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-25     Completed Date:  2009-04-02     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  334-41     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. skathiresan1@partners.org
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MeSH Terms
Descriptor/Qualifier:
Adult
Age of Onset
Algorithms
Case-Control Studies
Female
Gene Dosage*
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Mutation / physiology
Myocardial Infarction / epidemiology,  genetics*
Polymorphism, Single Nucleotide*
Risk Factors
Grant Support
ID/Acronym/Agency:
076113//Wellcome Trust; 089061//Wellcome Trust; K24 DK080140/DK/NIDDK NIH HHS; N01HD013107/HD/NICHD NIH HHS; P30ES007033/ES/NIEHS NIH HHS; R01 HL056931-02/HL/NHLBI NIH HHS; R01 HL056931-03/HL/NHLBI NIH HHS; R01 HL056931-04/HL/NHLBI NIH HHS; R01HL056931/HL/NHLBI NIH HHS; U54 RR020278/RR/NCRR NIH HHS; //British Heart Foundation; //Medical Research Council; //Wellcome Trust
Comments/Corrections
Erratum In:
Nat Genet. 2009 Jun;41(6):762
Note: Knouff, Christopher W [added]; Waterworth, Dawn M [added]; Walker, Max C [added]; Mooser, Vincent [added]

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