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Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies

Summary Background We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. Methods We did two genome-wide association studies (GWAS) with coronary angiographic phenotypi... Full description

Journal Title: The Lancet (British edition) 2011, Vol.377 (9763), p.383-392
Main Author: Reilly, Muredach P, Dr
Other Authors: Li, Mingyao, PhD , He, Jing, PhD , Ferguson, Jane F, PhD , Stylianou, Ioannis M, PhD , Mehta, Nehal N, MD , Burnett, Mary Susan, PhD , Devaney, Joseph M, PhD , Knouff, Christopher W, MD , Thompson, John R, Prof , Horne, Benjamin D, PhD , Stewart, Alexandre FR, PhD , Assimes, Themistocles L, MD , Wild, Philipp S, MD , Allayee, Hooman, PhD , Nitschke, Patrick Linsel, MD , Patel, Riyaz S, MD , Martinelli, Nicola, MD , Girelli, Domenico, Prof , Quyyumi, Arshed A, Prof , Anderson, Jeffrey L, Prof , Erdmann, Jeanette, Prof , Hall, Alistair S, MD , Schunkert, Heribert, Prof , Quertermous, Thomas, Prof , Blankenberg, Stefan, Prof , Hazen, Stanley L, Prof , Roberts, Robert, Prof , Kathiresan, Sekar, MD , Samani, Nilesh J, Prof , Epstein, Stephen E, Prof , Rader, Daniel J, Prof
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: Kidlington: Elsevier Ltd
ID: ISSN: 0140-6736
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3297116
title: Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
format: Article
creator:
  • Reilly, Muredach P, Dr
  • Li, Mingyao, PhD
  • He, Jing, PhD
  • Ferguson, Jane F, PhD
  • Stylianou, Ioannis M, PhD
  • Mehta, Nehal N, MD
  • Burnett, Mary Susan, PhD
  • Devaney, Joseph M, PhD
  • Knouff, Christopher W, MD
  • Thompson, John R, Prof
  • Horne, Benjamin D, PhD
  • Stewart, Alexandre FR, PhD
  • Assimes, Themistocles L, MD
  • Wild, Philipp S, MD
  • Allayee, Hooman, PhD
  • Nitschke, Patrick Linsel, MD
  • Patel, Riyaz S, MD
  • Martinelli, Nicola, MD
  • Girelli, Domenico, Prof
  • Quyyumi, Arshed A, Prof
  • Anderson, Jeffrey L, Prof
  • Erdmann, Jeanette, Prof
  • Hall, Alistair S, MD
  • Schunkert, Heribert, Prof
  • Quertermous, Thomas, Prof
  • Blankenberg, Stefan, Prof
  • Hazen, Stanley L, Prof
  • Roberts, Robert, Prof
  • Kathiresan, Sekar, MD
  • Samani, Nilesh J, Prof
  • Epstein, Stephen E, Prof
  • Rader, Daniel J, Prof
subjects:
  • ABO Blood-Group System - genetics
  • ADAM Proteins - genetics
  • ADAMTS7 Protein
  • Adult
  • Aged
  • Article
  • Atherosclerosis
  • Atherosclerosis (general aspects, experimental research)
  • Biological and medical sciences
  • Blood and lymphatic vessels
  • Cardiology. Vascular system
  • Cardiovascular disease
  • Coronary Angiography
  • Coronary Artery Disease - blood
  • Coronary Artery Disease - complications
  • Coronary Artery Disease - diagnostic imaging
  • Coronary Artery Disease - genetics
  • Coronary heart disease
  • Data collection
  • Design
  • Enzymes
  • Female
  • Gene Frequency
  • General aspects
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • grants
  • Heart
  • Heart attacks
  • Hospitals
  • Humans
  • Internal Medicine
  • Linkage Disequilibrium
  • Male
  • Medical imaging
  • Medical sciences
  • Middle Aged
  • myocardial infarction
  • Myocardial Infarction - blood
  • Myocardial Infarction - complications
  • Myocardial Infarction - diagnostic imaging
  • Myocardial Infarction - genetics
  • Polymorphism, Single Nucleotide
  • Risk assessment
  • Studies
ispartof: The Lancet (British edition), 2011, Vol.377 (9763), p.383-392
description: Summary Background We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. Methods We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). Findings In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10−13 ). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10−9 ). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Interpretation Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. Funding The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
url: Link


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titleIdentification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
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creatorReilly, Muredach P, Dr ; Li, Mingyao, PhD ; He, Jing, PhD ; Ferguson, Jane F, PhD ; Stylianou, Ioannis M, PhD ; Mehta, Nehal N, MD ; Burnett, Mary Susan, PhD ; Devaney, Joseph M, PhD ; Knouff, Christopher W, MD ; Thompson, John R, Prof ; Horne, Benjamin D, PhD ; Stewart, Alexandre FR, PhD ; Assimes, Themistocles L, MD ; Wild, Philipp S, MD ; Allayee, Hooman, PhD ; Nitschke, Patrick Linsel, MD ; Patel, Riyaz S, MD ; Martinelli, Nicola, MD ; Girelli, Domenico, Prof ; Quyyumi, Arshed A, Prof ; Anderson, Jeffrey L, Prof ; Erdmann, Jeanette, Prof ; Hall, Alistair S, MD ; Schunkert, Heribert, Prof ; Quertermous, Thomas, Prof ; Blankenberg, Stefan, Prof ; Hazen, Stanley L, Prof ; Roberts, Robert, Prof ; Kathiresan, Sekar, MD ; Samani, Nilesh J, Prof ; Epstein, Stephen E, Prof ; Rader, Daniel J, Prof
creatorcontribReilly, Muredach P, Dr ; Li, Mingyao, PhD ; He, Jing, PhD ; Ferguson, Jane F, PhD ; Stylianou, Ioannis M, PhD ; Mehta, Nehal N, MD ; Burnett, Mary Susan, PhD ; Devaney, Joseph M, PhD ; Knouff, Christopher W, MD ; Thompson, John R, Prof ; Horne, Benjamin D, PhD ; Stewart, Alexandre FR, PhD ; Assimes, Themistocles L, MD ; Wild, Philipp S, MD ; Allayee, Hooman, PhD ; Nitschke, Patrick Linsel, MD ; Patel, Riyaz S, MD ; Martinelli, Nicola, MD ; Girelli, Domenico, Prof ; Quyyumi, Arshed A, Prof ; Anderson, Jeffrey L, Prof ; Erdmann, Jeanette, Prof ; Hall, Alistair S, MD ; Schunkert, Heribert, Prof ; Quertermous, Thomas, Prof ; Blankenberg, Stefan, Prof ; Hazen, Stanley L, Prof ; Roberts, Robert, Prof ; Kathiresan, Sekar, MD ; Samani, Nilesh J, Prof ; Epstein, Stephen E, Prof ; Rader, Daniel J, Prof ; Wellcome Trust Case Control Consortium ; Myocardial Infarction Genetics Consortium
descriptionSummary Background We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. Methods We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). Findings In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10−13 ). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10−9 ). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Interpretation Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. Funding The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
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1EISSN: 1474-547X
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languageeng
publisherKidlington: Elsevier Ltd
subjectABO Blood-Group System - genetics ; ADAM Proteins - genetics ; ADAMTS7 Protein ; Adult ; Aged ; Article ; Atherosclerosis ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular disease ; Coronary Angiography ; Coronary Artery Disease - blood ; Coronary Artery Disease - complications ; Coronary Artery Disease - diagnostic imaging ; Coronary Artery Disease - genetics ; Coronary heart disease ; Data collection ; Design ; Enzymes ; Female ; Gene Frequency ; General aspects ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; grants ; Heart ; Heart attacks ; Hospitals ; Humans ; Internal Medicine ; Linkage Disequilibrium ; Male ; Medical imaging ; Medical sciences ; Middle Aged ; myocardial infarction ; Myocardial Infarction - blood ; Myocardial Infarction - complications ; Myocardial Infarction - diagnostic imaging ; Myocardial Infarction - genetics ; Polymorphism, Single Nucleotide ; Risk assessment ; Studies
ispartofThe Lancet (British edition), 2011, Vol.377 (9763), p.383-392
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6Burnett, Mary Susan, PhD
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11Stewart, Alexandre FR, PhD
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29Samani, Nilesh J, Prof
30Epstein, Stephen E, Prof
31Rader, Daniel J, Prof
32Wellcome Trust Case Control Consortium
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0Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
1The Lancet (British edition)
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descriptionSummary Background We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. Methods We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). Findings In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10−13 ). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10−9 ). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Interpretation Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. Funding The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
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12Coronary Angiography
13Coronary Artery Disease - blood
14Coronary Artery Disease - complications
15Coronary Artery Disease - diagnostic imaging
16Coronary Artery Disease - genetics
17Coronary heart disease
18Data collection
19Design
20Enzymes
21Female
22Gene Frequency
23General aspects
24Genetic Loci
25Genetic Predisposition to Disease
26Genome-Wide Association Study
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33Linkage Disequilibrium
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38myocardial infarction
39Myocardial Infarction - blood
40Myocardial Infarction - complications
41Myocardial Infarction - diagnostic imaging
42Myocardial Infarction - genetics
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44Risk assessment
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19Quyyumi, Arshed A, Prof
20Anderson, Jeffrey L, Prof
21Erdmann, Jeanette, Prof
22Hall, Alistair S, MD
23Schunkert, Heribert, Prof
24Quertermous, Thomas, Prof
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titleIdentification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
authorReilly, Muredach P, Dr ; Li, Mingyao, PhD ; He, Jing, PhD ; Ferguson, Jane F, PhD ; Stylianou, Ioannis M, PhD ; Mehta, Nehal N, MD ; Burnett, Mary Susan, PhD ; Devaney, Joseph M, PhD ; Knouff, Christopher W, MD ; Thompson, John R, Prof ; Horne, Benjamin D, PhD ; Stewart, Alexandre FR, PhD ; Assimes, Themistocles L, MD ; Wild, Philipp S, MD ; Allayee, Hooman, PhD ; Nitschke, Patrick Linsel, MD ; Patel, Riyaz S, MD ; Martinelli, Nicola, MD ; Girelli, Domenico, Prof ; Quyyumi, Arshed A, Prof ; Anderson, Jeffrey L, Prof ; Erdmann, Jeanette, Prof ; Hall, Alistair S, MD ; Schunkert, Heribert, Prof ; Quertermous, Thomas, Prof ; Blankenberg, Stefan, Prof ; Hazen, Stanley L, Prof ; Roberts, Robert, Prof ; Kathiresan, Sekar, MD ; Samani, Nilesh J, Prof ; Epstein, Stephen E, Prof ; Rader, Daniel J, Prof
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7Atherosclerosis (general aspects, experimental research)
8Biological and medical sciences
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11Cardiovascular disease
12Coronary Angiography
13Coronary Artery Disease - blood
14Coronary Artery Disease - complications
15Coronary Artery Disease - diagnostic imaging
16Coronary Artery Disease - genetics
17Coronary heart disease
18Data collection
19Design
20Enzymes
21Female
22Gene Frequency
23General aspects
24Genetic Loci
25Genetic Predisposition to Disease
26Genome-Wide Association Study
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29Heart attacks
30Hospitals
31Humans
32Internal Medicine
33Linkage Disequilibrium
34Male
35Medical imaging
36Medical sciences
37Middle Aged
38myocardial infarction
39Myocardial Infarction - blood
40Myocardial Infarction - complications
41Myocardial Infarction - diagnostic imaging
42Myocardial Infarction - genetics
43Polymorphism, Single Nucleotide
44Risk assessment
45Studies
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1Li, Mingyao, PhD
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4Stylianou, Ioannis M, PhD
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6Burnett, Mary Susan, PhD
7Devaney, Joseph M, PhD
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10Horne, Benjamin D, PhD
11Stewart, Alexandre FR, PhD
12Assimes, Themistocles L, MD
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14Allayee, Hooman, PhD
15Nitschke, Patrick Linsel, MD
16Patel, Riyaz S, MD
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19Quyyumi, Arshed A, Prof
20Anderson, Jeffrey L, Prof
21Erdmann, Jeanette, Prof
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24Quertermous, Thomas, Prof
25Blankenberg, Stefan, Prof
26Hazen, Stanley L, Prof
27Roberts, Robert, Prof
28Kathiresan, Sekar, MD
29Samani, Nilesh J, Prof
30Epstein, Stephen E, Prof
31Rader, Daniel J, Prof
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jtitleThe Lancet (British edition)
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Reilly, Muredach P, Dr
1Li, Mingyao, PhD
2He, Jing, PhD
3Ferguson, Jane F, PhD
4Stylianou, Ioannis M, PhD
5Mehta, Nehal N, MD
6Burnett, Mary Susan, PhD
7Devaney, Joseph M, PhD
8Knouff, Christopher W, MD
9Thompson, John R, Prof
10Horne, Benjamin D, PhD
11Stewart, Alexandre FR, PhD
12Assimes, Themistocles L, MD
13Wild, Philipp S, MD
14Allayee, Hooman, PhD
15Nitschke, Patrick Linsel, MD
16Patel, Riyaz S, MD
17Martinelli, Nicola, MD
18Girelli, Domenico, Prof
19Quyyumi, Arshed A, Prof
20Anderson, Jeffrey L, Prof
21Erdmann, Jeanette, Prof
22Hall, Alistair S, MD
23Schunkert, Heribert, Prof
24Quertermous, Thomas, Prof
25Blankenberg, Stefan, Prof
26Hazen, Stanley L, Prof
27Roberts, Robert, Prof
28Kathiresan, Sekar, MD
29Samani, Nilesh J, Prof
30Epstein, Stephen E, Prof
31Rader, Daniel J, Prof
aucorp
0Wellcome Trust Case Control Consortium
1Myocardial Infarction Genetics Consortium
formatjournal
genrearticle
ristypeJOUR
atitleIdentification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
jtitleThe Lancet (British edition)
addtitleLancet
date2011
risdate2011
volume377
issue9763
spage383
epage392
pages383-392
issn0140-6736
eissn1474-547X
codenLANCAO
notes
0Authors contributed equally
1Webappendix shows full listing of participants from the Wellcome Trust Case Control Consortium (WTCCC) and the Myocardial Infarction Genetics (MI-GEN) Consortium
abstractSummary Background We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. Methods We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). Findings In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10−13 ). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10−9 ). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Interpretation Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. Funding The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
copKidlington
pubElsevier Ltd
pmid21239051
doi10.1016/S0140-6736(10)61996-4
oafree_for_read