Additive Effect of Multiple Genetic Variants on the Risk of Coronary Artery Disease

被引:25
作者
Lluis-Ganella, Carla [1 ]
Lucas, Gavin [1 ]
Subirana, Isaac [1 ,2 ]
Senti, Mariano [1 ,3 ]
Jimenez-Conde, Jordi [4 ]
Marrugat, Jaume [1 ]
Tomas, Marta [1 ]
Elosua, Roberto [1 ,2 ]
机构
[1] IMIM Hosp Mar, Inst Municipal Invest Med, Grp Epidemiol & Genet Cardiovasc EGEC ULEC, Barcelona 08003, Spain
[2] CIBERESP, Barcelona, Spain
[3] Univ Pompeu Fabra, Barcelona, Spain
[4] Hosp Mar, Serv Neurol, Barcelona, Spain
来源
REVISTA ESPANOLA DE CARDIOLOGIA | 2010年 / 63卷 / 08期
关键词
Coronary artery disease; Genetics; Polymorphisms; Genetic risk; Genetic variants; GENOME-WIDE ASSOCIATION; CARDIOVASCULAR EVENTS; ATHEROSCLEROSIS RISK; CHROMOSOME; 9P21.3; LOCUS; COMMUNITIES; PREDICTION; IMPACT; WOMEN; SCORE;
D O I
10.1016/S0300-8932(10)70204-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction and objectives. Coronary artery disease (CAD) has a substantial genetic component and, in recent years, a number of genetic variants associated with the disease have been identified. The objective of this study was to evaluate the magnitude of the association between a genetic risk score, which is based on the accumulated number of risk alleles in all genetic variants of interest, and the presence of CAD. Methods. The study involved in silico data from the Wellcome Trust Case-Control Consortium on 1988 patients with CAD and 5380 controls. The association between the genetic risk score and CAD was assessed using logistic regression analysis. Results. Nine genetic variants independently associated with CAD irrespective of other cardiovascular risk factors were selected. There was a linear association between the number of risk alleles and the risk of presenting with CAD (odds ratio [OR] for an increase of one allele=1.18; 95% confidence interval [CI], 1.15-1.22; P=2 x 10(-16)). The OR for CAD for the last quintile of the accumulated number of risk alleles relative to the first was 2.21 (95% Cl, 1.87-2.61; P=5 x 10(-21)). Conclusions. A genetic risk score based on nine genetic variants independently associated with CAD irrespective of other cardiovascular risk factors was associated with the presence of the disease. Cohort studies are needed to determine whether this genetic risk score can improve the predictive capacity or the risk classification of classical risk functions.
引用
收藏
页码:925 / 933
页数:9
相关论文
共 25 条
[11]  
Hindorff L., CATALOG PUBLISHED GE
[12]  
Hlatky Mark A, 2009, Circulation, V119, P2408, DOI 10.1161/CIRCULATIONAHA.109.192278
[13]   Polymorphisms associated with cholesterol and risk of cardiovascular events [J].
Kathiresan, Sekar ;
Melander, Olle ;
Anevski, Dragi ;
Guiducci, Candace ;
Burtt, Noel P. ;
Roos, Charlotta ;
Hirschhorn, Joel N. ;
Berglund, Goran ;
Hedblad, Bo ;
Groop, Leif ;
Altshuler, David M. ;
Newton-Cheh, Christopher ;
Orho-Melander, Marju .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (12) :1240-1249
[14]   Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants [J].
Kathiresan, Sekar ;
Altschuler, David ;
Anand, Sonia ;
Ardissino, Diego ;
Asselta, Rosanna ;
Ball, Stephen G. ;
Balmforth, Anthony J. ;
Berger, Klaus ;
Berglund, Goran ;
Bernardi, Francesco ;
Bernardinelli, Luisa ;
Berzuini, Carlo ;
Braund, Peter S. ;
Burnett, Mary-Susan ;
Burtt, Noel ;
Cambien, Francois ;
Casari, Giorgio ;
Celli, Patrizia ;
Chen, Zhen ;
Corrocher, Roberto ;
Daly, Mark J. ;
Deloukas, Panos ;
Devaney, Joe ;
Do, Ron ;
Duga, Stefano ;
Elosua, Roberto ;
Engert, James C. ;
Epstein, Stephen E. ;
Erdmann, Jeanette ;
Ferrario, Maurizio ;
Fetiveau, Raffaela ;
Fischer, Marcus ;
Friedlander, Yechiel ;
Gabriel, Stacey B. ;
Galli, Michele ;
Gianniny, Lauren ;
Girelli, Domenico ;
Grosshennig, Anika ;
Guiducci, Candace ;
Hakonarson, Hakon H. ;
Hall, Alistair S. ;
Havulinna, Aki S. ;
Hengstenberg, Christian ;
Hirschhorn, Joel N. ;
Holm, Hilma ;
Huge, Andreas ;
Kent, Kenneth M. ;
Konig, Inke R. ;
Korn, Joshua M. ;
Li, Mingyao .
NATURE GENETICS, 2009, 41 (03) :334-341
[15]   Coronary risk estimation in Spain using a calibrated Framingham function [J].
Marrugat, J ;
Solanas, P ;
D'Agostino, R ;
Sullivan, L ;
Ordovas, J ;
Cordón, F ;
Ramos, R ;
Sala, J ;
Masià, R ;
Rohlfs, I ;
Elosua, R ;
Kannel, WB .
REVISTA ESPANOLA DE CARDIOLOGIA, 2003, 56 (03) :253-261
[16]   An adaptation of the Framingham coronary heart disease risk function to European Mediterranean areas [J].
Marrugat, J ;
D'Agostino, R ;
Sullivan, L ;
Elosua, R ;
Wilson, P ;
Ordovas, J ;
Solanas, P ;
Cordón, F ;
Ramos, R ;
Sala, J ;
Masiá, R ;
Kannel, WB .
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH, 2003, 57 (08) :634-638
[17]   A common allele on chromosome 9 associated with coronary heart disease [J].
McPherson, Ruth ;
Pertsemlidis, Alexander ;
Kavaslar, Nihan ;
Stewart, Alexandre F. R. ;
Roberts, Robert ;
Cox, David R. ;
Hinds, David A. ;
Pennacchio, Len A. ;
Tybjaerg-Hansen, Anne ;
Folsom, Aaron R. ;
Boerwinkle, Eric ;
Hobbs, Helen H. ;
Cohen, Jonathan C. .
SCIENCE, 2007, 316 (5830) :1488-1491
[18]   Prediction of coronary heart disease risk using a genetic risk score: The atherosclerosis risk in communities study [J].
Morrison, Alanna C. ;
Bare, Lance A. ;
Chambless, Lloyd E. ;
Ellis, Stephen G. ;
Malloy, Mary ;
Kane, John P. ;
Pankow, James S. ;
Devlin, James J. ;
Willerson, James T. ;
Boerwinkle, Eric .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2007, 166 (01) :28-35
[19]   Genome-wide association study identifies eight loci associated with blood pressure [J].
Newton-Cheh, Christopher ;
Johnson, Toby ;
Gateva, Vesela ;
Tobin, Martin D. ;
Bochud, Murielle ;
Coin, Lachlan ;
Najjar, Samer S. ;
Zhao, Jing Hua ;
Heath, Simon C. ;
Eyheramendy, Susana ;
Papadakis, Konstantinos ;
Voight, Benjamin F. ;
Scott, Laura J. ;
Zhang, Feng ;
Farrall, Martin ;
Tanaka, Toshiko ;
Wallace, Chris ;
Chambers, John C. ;
Khaw, Kay-Tee ;
Nilsson, Peter ;
van der Harst, Pim ;
Polidoro, Silvia ;
Grobbee, Diederick E. ;
Onland-Moret, N. Charlotte ;
Bots, Michiel L. ;
Wain, Louise V. ;
Elliott, Katherine S. ;
Teumer, Alexander ;
Luan, Jian'an ;
Lucas, Gavin ;
Kuusisto, Johanna ;
Burton, Paul R. ;
Hadley, David ;
McArdle, Wendy L. ;
Brown, Morris ;
Dominiczak, Anna ;
Newhouse, Stephen J. ;
Samani, Nilesh J. ;
Webster, John ;
Zeggini, Eleftheria ;
Beckmann, Jacques S. ;
Bergmann, Sven ;
Lim, Noha ;
Song, Kijoung ;
Vollenweider, Peter ;
Waeber, Gerard ;
Waterworth, Dawn M. ;
Yuan, Xin ;
Groop, Leif ;
Orho-Melander, Marju .
NATURE GENETICS, 2009, 41 (06) :666-676
[20]   Association Between a Literature-Based Genetic Risk Score and Cardiovascular Events in Women [J].
Paynter, Nina P. ;
Chasman, Daniel I. ;
Pare, Guillaume ;
Buring, Julie E. ;
Cook, Nancy R. ;
Miletich, Joseph P. ;
Ridker, Paul M. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2010, 303 (07) :631-637