Document Detail


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.
MedLine Citation:
PMID:  21239051     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Muredach P Reilly; Mingyao Li; Jing He; Jane F Ferguson; Ioannis M Stylianou; Nehal N Mehta; Mary Susan Burnett; Joseph M Devaney; Christopher W Knouff; John R Thompson; Benjamin D Horne; Alexandre F R Stewart; Themistocles L Assimes; Philipp S Wild; Hooman Allayee; Patrick Linsel Nitschke; Riyaz S Patel; ; ; Nicola Martinelli; Domenico Girelli; Arshed A Quyyumi; Jeffrey L Anderson; Jeanette Erdmann; Alistair S Hall; Heribert Schunkert; Thomas Quertermous; Stefan Blankenberg; Stanley L Hazen; Robert Roberts; Sekar Kathiresan; Nilesh J Samani; Stephen E Epstein; Daniel J Rader
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-14
Journal Detail:
Title:  Lancet     Volume:  377     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-31     Completed Date:  2011-02-23     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  383-92     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
ABO Blood-Group System / genetics*
ADAM Proteins / genetics*
Adult
Aged
Coronary Angiography
Coronary Artery Disease / blood,  complications,  genetics*,  radiography
Female
Gene Frequency
Genetic Loci*
Genetic Predisposition to Disease
Genome-Wide Association Study*
Humans
Linkage Disequilibrium
Male
Middle Aged
Myocardial Infarction / blood,  complications,  genetics*,  radiography
Polymorphism, Single Nucleotide*
Grant Support
ID/Acronym/Agency:
090532//Wellcome Trust; 091157//Wellcome Trust; 1P01 HL098055-01/HL/NHLBI NIH HHS; CZB/4/540//Chief Scientist Office; ETM/137//Chief Scientist Office; ETM/75//Chief Scientist Office; G0600329//Medical Research Council; G0800759//Medical Research Council; HL087647/HL/NHLBI NIH HHS; K23 HL097151/HL/NHLBI NIH HHS; KL2 RR024132/RR/NCRR NIH HHS; KL2 RR024132-06/RR/NCRR NIH HHS; MOP-82810//Canadian Institutes of Health Research; MOP172605//Canadian Institutes of Health Research; MOP77682//Canadian Institutes of Health Research; P01 HL076491/HL/NHLBI NIH HHS; P01 HL076491-06/HL/NHLBI NIH HHS; P01 HL076491-06A1/HL/NHLBI NIH HHS; P01 HL076491-07/HL/NHLBI NIH HHS; P01 HL098055/HL/NHLBI NIH HHS; P01 HL098055-01A1/HL/NHLBI NIH HHS; P01 HL098055-02/HL/NHLBI NIH HHS; R01 DK071224/DK/NIDDK NIH HHS; R01 HL087647/HL/NHLBI NIH HHS; R01 HL087676/HL/NHLBI NIH HHS; R01- HL071878/HL/NHLBI NIH HHS; U54 RR020278/RR/NCRR NIH HHS; //British Heart Foundation; //Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/ABO Blood-Group System; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS7 protein, human
Investigator
Investigator/Affiliation:
Atif N Qasim / ; Stephanie L DerOhannessian / ; Liming Qu / ; Thomas P Cappola / ; Zhen Chen / ; William Matthai / ; Hakoh H Hakonarson / ; Robert Wilensky / ; Kenneth M Kent / ; Joseph M Lindsay / ; Augusto D Pichard / ; Lowell Satler / ; Ron Waksman / ; Christopher W Knoupf / ; Max C Walker / ; Dawn M Waterworth / ; Vincent Mosser / ; John R Thompson / ; Peter S Braund / ; Benjamin Wright / ; Anthony J Balmforth / ; Stephen G Ball / ; Alistair S Hall / ; Nilesh J Samani / ; Alexandre F R Stewart / ; Li Chen / ; George A Wells / ; Ruth McPherson / ; Robert Roberts / ; Philipps S Wild / ; Karl Lackner / ; Thomas F Munzel / ; Arne Schillert / ; Renate Schnabel / ; Tanja Zeller / ; Andreas Ziegler / ; Stefan Blankenberg / ; Themistocles L Assimes / ; Devin Absher / ; Mark A Hlatky / ; Carlos Iribaren / ; Joshua W Knowles / ; Thomas Quertermous / ; Sekar Kathiresan / ; Patrick Linsel-Nitschke / ; Inke R König / ; Christian Hengstenberg / ; Janja Nahrstaedt / ; Annette Peters / ; Stefan Schreiber / ; Erich Wichmann / ; Christina Willenborg / ; Jeanette Erdmann / ; Hribert Schunkert / ; Riyaz S Patel / ; Shaoyong Su / ; Mark Bouzyk / ; Viola Vaccarino / ; Abelmard M Zafari / ; Arshed A Quyyumi / ; Benjamin D Horne / ; John F Carlquist / ; Joseph B Muhlestein / ; Jeffrey L Anderson / ; Nicola Martinelli / ; Oliviero Olivieri / ; Domenico Girelli / ; John Barnard / ; Hooman Allayee / ; Jaana Hartiala / ; W H Wilson Tang / ; Stanley L Hazen / ; Paul R Burton / ; David G Clayton / ; Lon R Cardon / ; Nick Craddock / ; Panos Deloukas / ; Audrey Duncanson / ; Dominic P Kwiatkowski / ; Mark I McCarthy / ; Willem H Ouwehand / ; Nilesh J Samani / ; John A Todd / ; Peter Donnelly / ; Jeffrey C Barrett / ; Paul R Burton / ; Dan Davison / ; Peter Donnelly / ; Doug Easton / ; David M Evans / ; Hin-Tak Leung / ; Jonathan L Marchini / ; Andrew P Morris / ; Chris C A Spencer / ; Martin D Tobin / ; Lon R Cardon / ; David G Clayton / ; Antony P Attwood / ; James P Boorman / ; Barbara Cant / ; Ursula Everson / ; Judith M Hussey / ; Jennifer D Jolley / ; Alexandra S Knight / ; Kerstin Koch / ; Elizabeth Meech / ; Sarah Nutland / ; Christopher V Prowse / ; Helen E Stevens / ; Niall C Taylor / ; Graham R Walters / ; Neil M Walker / ; Nicholas A Watkins / ; Thilo Winzer / ; John A Todd / ; Willem H Ouwehand / ; Richard W Jones / ; Wendy L McArdle / ; Susan M Ring / ; David P Strachan / ; Marcus Pembrey / ; Gerome Breen / ; David St Clair / ; Sian Caesar / ; Katherine Gordon-Smith / ; Lisa Jones / ; Christine Fraser / ; Elaine K Green / ; Detelina Grozeva / ; Marian L Hamshere / ; Peter A Holmans / ; Ian R Jones / ; George Kirov / ; Valentina Moskvina / ; Ivan Nikolov / ; Michael C O'Donovan / ; Michael J Owen / ; Nick Craddock / ; David A Collier / ; Amanda Elkin / ; Anne Farmer / ; Richard Williamson / ; Peter McGuffin / ; Allan H Young / ; I Nicol Ferrier / ; Stephen G Ball / ; Anthony J Balmforth / ; Jennifer H Barrett / ; D Timothy Bishop / ; Mark M Iles / ; Azhar Maqbool / ; Nadira Yuldasheva / ; Alistair S Hall / ; Peter S Braund / ; Paul R Burton / ; Richard J Dixon / ; Massimo Mangino / ; Suzanne Stevens / ; Martin D Tobin / ; John R Thompson / ; Nilesh J Samani / ; Francesca Bredin / ; Mark Tremelling / ; Miles Parkes / ; Hazel Drummond / ; Charles W Lees / ; Elaine R Nimmo / ; Jack Satsangi / ; Sheila A Fisher / ; Alastair Forbes / ; Cathryn M Lewis / ; Clive M Onnie / ; Natalie J Prescott / ; Jeremy Sanderson / ; Christopher G Mathew / ; Jamie Barbour / ; M Khalid Mohiuddin / ; Catherine E Todhunter / ; John C Mansfield / ; Tariq Ahmad / ; Fraser R Cummings / ; Derek P Jewell / ; John Webster / ; Morris J Brown / ; David G Clayton / ; Mark Lathrop / ; John Connell / ; Anna Dominiczak / ; Nilesh J Samani / ; Carolina A Braga Marcano / ; Beverley Burke / ; Richard Dobson / ; Johannie Gungadoo / ; Kate L Lee / ; Patricia B Munroe / ; Stephen J Newhouse / ; Abiodun Onipinla / ; Chris Wallace / ; Mingzhan Xue / ; Mark Caulfield / ; Martin Farrall / ; Anne Barton / ; Ian N Bruce / ; Hannah Donovan / ; Steve Eyre / ; Paul D Gilbert / ; Samantha L Hider / ; Anne M Hinks / ; Sally L John / ; Catherine Potter / ; Alan J Silman / ; Deborah P M Symmons / ; Wendy Thomson / ; Jane Worthington / ; David G Clayton / ; David B Dunger / ; Sarah Nutland / ; Helen E Stevens / ; Neil M Walker / ; Barry Widmer / ; John A Todd / ; Timothy M Frayling / ; Rachel M Freathy / ; Hana Lango / ; John R B Perry / ; Beverley M Shields / ; Michael N Weedon / ; Andrew T Hattersley / ; Graham A Hitman / ; Mark Walker / ; Kate S Elliott / ; Christopher J Groves / ; Cecilia M Lindgren / ; Nigel W Rayner / ; Nicholas J Timpson / ; Eleftheria Zeggini / ; Mark I McCarthy / ; Melanie Newport / ; Giorgio Sirugo / ; Emily Lyons / ; Fredrik Vannberg / ; Adrian V S Hill / ; Linda A Bradbury / ; Claire Farrar / ; Jennifer J Pointon / ; Paul Wordsworth / ; Matthew A Brown / ; Jayne A Franklyn / ; Joanne M Heward / ; Matthew J Simmonds / ; Stephen C L Gough / ; Sheila Seal / ; Michael R Stratton / ; Nazneen Rahman / ; Maria Ban / ; An Goris / ; Stephen J Sawcer / ; Alastair Compston / ; David Conway / ; Muminatou Jallow / ; Melanie Newport / ; Giorgio Sirugo / ; Kirk A Rockett / ; Dominic P Kwiatkowski / ; Suzannah J Bumpstead / ; Amy Chaney / ; Kate Downes / ; Mohammed J R Ghori / ; Rhian Gwilliam / ; Sarah E Hunt / ; Michael Inouye / ; Andrew Keniry / ; Emma King / ; Ralph McGinnis / ; Simon Potter / ; Rathi Ravindrarajah / ; Pamela Whittaker / ; Claire Widden / ; David Withers / ; Panos Deloukas / ; Hin-Tak Leung / ; Sarah Nutland / ; Helen E Stevens / ; Neil M Walker / ; John A Todd / ; Doug Easton / ; David G Clayton / ; Paul R Burton / ; Martin D Tobin / ; Jeffrey C Barrett / ; David M Evans / ; Andrew P Morris / ; Lon R Cardon / ; Niall J Cardin / ; Dan Davison / ; Teresa Ferreira / ; Joanne Pereira-Gale / ; Ingeleif B Hallgrimsdóttir / ; Bryan N Bowie / ; Jonathan L Marchini / ; Chris C A Spencer / ; Zhan Su / ; Yik Ying Teo / ; Damjan Vukcevic / ; Peter Donnelly / ; David Bentley / ; Matthew A Brown / ; Lon R Cardon / ; Mark Caulfield / ; David G Clayton / ; Alistair Compston / ; Nick Craddock / ; Panos Deloukas / ; Peter Donnelly / ; Martin Farrall / ; Stephen C L Gough / ; Alistair S Hall / ; Andrew T Hattersley / ; Adrian V S Hill / ; Dominic P Kwiatkowski / ; Christopher G Mathew / ; Mark I McCarthy / ; Willem H Ouwehand / ; Miles Parkes / ; Marcus Pembrey / ; Nazneen Rahman / ; Nilesh J Samani / ; Michael R Stratton / ; John A Todd / ; Jane Worthington / ; Sekar Kathiresan / ; James B Meigs / ; Gordon Williams / ; David M Nathan / ; Calum A MacRae / ; Christopher J O'Donnell / ; Diego Ardissino / ; Pier Angelia 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 / ; 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 / ; 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 /
Comments/Corrections
Comment In:
Lancet. 2011 Jan 29;377(9763):356-8   [PMID:  21239053 ]
Lancet. 2011 Apr 30;377(9776):1493; author reply 1493-4   [PMID:  21531266 ]
Lancet. 2011 Apr 30;377(9776):1492-3; author reply 1493-4   [PMID:  21531265 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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