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
[1]   Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts [J].
Aulchenko, Yurii S. ;
Ripatti, Samuli ;
Lindqvist, Ida ;
Boomsma, Dorret ;
Heid, Iris M. ;
Pramstaller, Peter P. ;
Penninx, Brenda W. J. H. ;
Janssens, A. Cecile J. W. ;
Wilson, James F. ;
Spector, Tim ;
Martin, Nicholas G. ;
Pedersen, Nancy L. ;
Kyvik, Kirsten Ohm ;
Kaprio, Jaakko ;
Hofman, Albert ;
Freimer, Nelson B. ;
Jarvelin, Marjo-Riitta ;
Gyllensten, Ulf ;
Campbell, Harry ;
Rudan, Igor ;
Johansson, Asa ;
Marroni, Fabio ;
Hayward, Caroline ;
Vitart, Veronique ;
Jonasson, Inger ;
Pattaro, Cristian ;
Wright, Alan ;
Hastie, Nick ;
Pichler, Irene ;
Hicks, Andrew A. ;
Falchi, Mario ;
Willemsen, Gonneke ;
Hottenga, Jouke-Jan ;
de Geus, Eco J. C. ;
Montgomery, Grant W. ;
Whitfield, John ;
Magnusson, Patrik ;
Saharinen, Juha ;
Perola, Markus ;
Silander, Kaisa ;
Isaacs, Aaron ;
Sijbrands, Eric J. G. ;
Uitterlinden, Andre G. ;
Witteman, Jacqueline C. M. ;
Oostra, Ben A. ;
Elliott, Paul ;
Ruokonen, Aimo ;
Sabatti, Chiara ;
Gieger, Christian ;
Meitinger, Thomas .
NATURE GENETICS, 2009, 41 (01) :47-55
[2]   Impact of Adding a Single Allele in the 9p21 Locus to Traditional Risk Factors on Reclassification of Coronary Heart Disease Risk and Implications for Lipid-Modifying Therapy in the Atherosclerosis Risk in Communities Study [J].
Brautbar, Ariel ;
Ballantyne, Christie M. ;
Lawson, Kim ;
Nambi, Vijay ;
Chambless, Lloyd ;
Folsom, Aaron R. ;
Willerson, James T. ;
Boerwinkle, Eric .
CIRCULATION-CARDIOVASCULAR GENETICS, 2009, 2 (03) :279-U175
[3]   Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].
Burton, Paul R. ;
Clayton, David G. ;
Cardon, Lon R. ;
Craddock, Nick ;
Deloukas, Panos ;
Duncanson, Audrey ;
Kwiatkowski, Dominic P. ;
McCarthy, Mark I. ;
Ouwehand, Willem H. ;
Samani, Nilesh J. ;
Todd, John A. ;
Donnelly, Peter ;
Barrett, Jeffrey C. ;
Davison, Dan ;
Easton, Doug ;
Evans, David ;
Leung, Hin-Tak ;
Marchini, Jonathan L. ;
Morris, Andrew P. ;
Spencer, Chris C. A. ;
Tobin, Martin D. ;
Attwood, Antony P. ;
Boorman, James P. ;
Cant, Barbara ;
Everson, Ursula ;
Hussey, Judith M. ;
Jolley, Jennifer D. ;
Knight, Alexandra S. ;
Koch, Kerstin ;
Meech, Elizabeth ;
Nutland, Sarah ;
Prowse, Christopher V. ;
Stevens, Helen E. ;
Taylor, Niall C. ;
Walters, Graham R. ;
Walker, Neil M. ;
Watkins, Nicholas A. ;
Winzer, Thilo ;
Jones, Richard W. ;
McArdle, Wendy L. ;
Ring, Susan M. ;
Strachan, David P. ;
Pembrey, Marcus ;
Breen, Gerome ;
St Clair, David ;
Caesar, Sian ;
Gordon-Smith, Katherine ;
Jones, Lisa ;
Fraser, Christine ;
Green, Elain K. .
NATURE, 2007, 447 (7145) :661-678
[4]   Joint Effects of Common Genetic Variants on the Risk for Type 2 Diabetes in U. S. Men and Women of European Ancestry [J].
Cornelis, Marilyn C. ;
Qi, Lu ;
Zhang, Cuilin ;
Kraft, Peter ;
Manson, JoAnn ;
Cai, Tianxi ;
Hunter, David J. ;
Hu, Frank B. .
ANNALS OF INTERNAL MEDICINE, 2009, 150 (08) :541-W98
[5]   New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk [J].
Dupuis, Josee ;
Langenberg, Claudia ;
Prokopenko, Inga ;
Saxena, Richa ;
Soranzo, Nicole ;
Jackson, Anne U. ;
Wheeler, Eleanor ;
Glazer, Nicole L. ;
Bouatia-Naji, Nabila ;
Gloyn, Anna L. ;
Lindgren, Cecilia M. ;
Magi, Reedik ;
Morris, Andrew P. ;
Randall, Joshua ;
Johnson, Toby ;
Elliott, Paul ;
Rybin, Denis ;
Thorleifsson, Gudmar ;
Steinthorsdottir, Valgerdur ;
Henneman, Peter ;
Grallert, Harald ;
Dehghan, Abbas ;
Hottenga, Jouke Jan ;
Franklin, Christopher S. ;
Navarro, Pau ;
Song, Kijoung ;
Goel, Anuj ;
Perry, John R. B. ;
Egan, Josephine M. ;
Lajunen, Taina ;
Grarup, Niels ;
Sparso, Thomas ;
Doney, Alex ;
Voight, Benjamin F. ;
Stringham, Heather M. ;
Li, Man ;
Kanoni, Stavroula ;
Shrader, Peter ;
Cavalcanti-Proenca, Christine ;
Kumari, Meena ;
Qi, Lu ;
Timpson, Nicholas J. ;
Gieger, Christian ;
Zabena, Carina ;
Rocheleau, Ghislain ;
Ingelsson, Erik ;
An, Ping ;
O'Connell, Jeffrey ;
Luan, Jian'an ;
Elliott, Amanda .
NATURE GENETICS, 2010, 42 (02) :105-U32
[6]  
Elosua R, 2009, REV ESP CARDIOL, p24B
[7]   New susceptibility locus for coronary artery disease on chromosome 3q22.3 [J].
Erdmann, Jeanette ;
Grosshennig, Anika ;
Braund, Peter S. ;
Koenig, Inke R. ;
Hengstenberg, Christian ;
Hall, Alistair S. ;
Linsel-Nitschke, Patrick ;
Kathiresan, Sekar ;
Wright, Ben ;
Tregouet, David-Alexandre ;
Cambien, Francois ;
Bruse, Petra ;
Aherrahrou, Zouhair ;
Wagner, Arnika K. ;
Stark, Klaus ;
Schwartz, Stephen M. ;
Salomaa, Veikko ;
Elosua, Roberto ;
Melander, Olle ;
Voight, Benjamin F. ;
O'Donnell, Christopher J. ;
Peltonen, Leena ;
Siscovick, David S. ;
Altshuler, David ;
Merlini, Piera Angelica ;
Peyvandi, Flora ;
Bernardinelli, Luisa ;
Ardissino, Diego ;
Schillert, Arne ;
Blankenberg, Stefan ;
Zeller, Tanja ;
Wild, Philipp ;
Schwarz, Daniel F. ;
Tiret, Laurence ;
Perret, Claire ;
Schreiber, Stefan ;
El Mokhtari, Nour Eddine ;
Schaefer, Arne ;
Maerz, Winfried ;
Renner, Wilfried ;
Bugert, Peter ;
Klueter, Harald ;
Schrezenmeir, Juergen ;
Rubin, Diana ;
Ball, Stephen G. ;
Balmforth, Anthony J. ;
Wichmann, H-Erich ;
Meitinger, Thomas ;
Fischer, Marcus ;
Meisinger, Christa .
NATURE GENETICS, 2009, 41 (03) :280-282
[8]   The search for new cardiovascular biomarkers [J].
Gerszten, Robert E. ;
Wang, Thomas J. .
NATURE, 2008, 451 (7181) :949-952
[9]   SNPassoc:: an R package to perform whole genome association studies [J].
Gonzalez, Juan R. ;
Armengol, Lluis ;
Sole, Xavier ;
Guino, Elisabet ;
Mercader, Josep M. ;
Estivill, Xavier ;
Moreno, Victor .
BIOINFORMATICS, 2007, 23 (05) :644-645
[10]   A common variant on chromosome 9p21 affects the risk of myocardial infarction [J].
Helgadottir, Anna ;
Thorleifsson, Gudmar ;
Manolescu, Andrei ;
Gretarsdottir, Solveig ;
Blondal, Thorarinn ;
Jonasdottir, Aslaug ;
Jonasdottir, Adalbjorg ;
Sigurdsson, Asgeir ;
Baker, Adam ;
Palsson, Arnar ;
Masson, Gisli ;
Gudbjartsson, Daniel F. ;
Magnusson, Kristinn P. ;
Andersen, Karl ;
Levey, Allan I. ;
Backman, Valgerdur M. ;
Matthiasdottir, Sigurborg ;
Jonsdottir, Thorbjorg ;
Palsson, Stefan ;
Einarsdottir, Helga ;
Gunnarsdottir, Steinunn ;
Gylfason, Arnaldur ;
Vaccarino, Viola ;
Hooper, W. Craig ;
Reilly, Muredach P. ;
Granger, Christopher B. ;
Austin, Harland ;
Rader, Daniel J. ;
Shah, Svati H. ;
Quyyumi, Arshed A. ;
Gulcher, Jeffrey R. ;
Thorgeirsson, Gudmundur ;
Thorsteinsdottir, Unnur ;
Kong, Augustine ;
Stefansson, Kari .
SCIENCE, 2007, 316 (5830) :1491-1493