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PMID: 19198609 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 41 ·No. 3 ·2009-03-00 ·Pages 334-41

Myocardial Infarction Genetics Consortium, Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Samani NJ, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Kathiresan S, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Kathiresan S, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Voight BF, Purcell S, Nemesh J, Korn JM, McCarroll SA, Schwartz SM, Yee J, Kathiresan S, Lucas G, Subirana I, Elosua R, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, Samani NJ, Thompson JR, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall A, Wellcome Trust Case Control Consortium, Schunkert H, Erdmann J, Linsel-Nitschke P, Lieb W, Ziegler A, König I, Hengstenberg C, Fischer M, Stark K, Grosshennig A, Preuss M, Wichmann HE, Schreiber S, Schunkert H, Samani NJ, Erdmann J, Ouwehand W, Hengstenberg C, Deloukas P, Scholz M, Cambien F, Reilly MP, Li M, Chen Z, Wilensky R, Matthai W, Qasim A, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Scheffold T, Berger K, Stoll M, Huge A, Girelli D, Martinelli N, Olivieri O, Corrocher R, Morgan T, Spertus JA, McKeown P, Patterson CC, Schunkert H, Erdmann E, Linsel-Nitschke P, Lieb W, Ziegler A, König IR, Hengstenberg C, Fischer M, Stark K, Grosshennig A, Preuss M, Wichmann HE, Schreiber S, Hólm H, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Engert JC, Do R, Xie C, Anand S, Kathiresan S, Ardissino D, Mannucci PM, Siscovick D, O'Donnell CJ, Samani NJ, Melander O, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Altshuler D

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.

MeSH Terms
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
Authors & Affiliations
188 authors, click to expand affiliations / ORCID
Myocardial Infarction Genetics Consortium
Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [email protected]
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
Wellcome Trust Case Control Consortium
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
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
Published
2009-03-00
Epub
2009-00-08
Pages
334-41
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2681011
Subset
IM
Grants
NHLBI NIH HHS · R01 HL056931-02 · United States
Medical Research Council · G0802320 · United Kingdom
British Heart Foundation · United Kingdom
NCRR NIH HHS · U54 RR020278 · United States
NIDDK NIH HHS · K24 DK080140 · United States
NICHD NIH HHS · N01HD013107 · United States
NHLBI NIH HHS · R01 HL056931-04 · United States
NHLBI NIH HHS · R01HL056931 · United States
NHLBI NIH HHS · R01 HL056931-03 · United States
Wellcome Trust · 089061 · United Kingdom
NIEHS NIH HHS · P30ES007033 · United States
Wellcome Trust · 076113 · United Kingdom
Corrections
ErratumIn
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