Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

被引:176
作者
Bis, Joshua C. [1 ,2 ]
Kavousi, Maryam [3 ,4 ]
Franceschini, Nora [5 ]
Isaacs, Aaron [6 ,7 ]
Abecasis, Goncalo R. [8 ]
Schminke, Ulf [9 ]
Post, Wendy S. [10 ]
Smith, Albert V. [11 ]
Cupples, L. Adrienne [12 ,13 ]
Markus, Hugh S. [14 ]
Schmidt, Reinhold [15 ]
Huffman, Jennifer E. [16 ]
Lehtimaki, Terho [17 ,18 ]
Baumert, Jens [19 ]
Muenzel, Thomas [20 ]
Heckbert, Susan R. [1 ,21 ,22 ]
Dehghan, Abbas [3 ,4 ]
North, Kari [23 ]
Oostra, Ben [7 ,24 ]
Bevan, Steve [14 ]
Stoegerer, Eva-Maria [15 ]
Hayward, Caroline [16 ]
Raitakari, Olli [25 ,26 ]
Meisinger, Christa [19 ]
Schillert, Arne [27 ]
Sanna, Serena [28 ]
Voelzke, Henry [29 ]
Cheng, Yu-Ching [30 ]
Thorsson, Bolli [11 ]
Fox, Caroline S. [13 ,31 ,32 ]
Rice, Kenneth [33 ]
Rivadeneira, Fernando [4 ,34 ]
Nambi, Vijay [35 ,36 ,37 ]
Halperin, Eran [38 ,39 ]
Petrovic, Katja E. [40 ,41 ]
Peltonen, Leena [42 ,43 ,44 ]
Wichmann, H. Erich [45 ]
Schnabel, Renate B. [20 ]
Doerr, Marcus [46 ]
Parsa, Afshin [47 ]
Aspelund, Thor [11 ,48 ]
Demissie, Serkalem [12 ]
Kathiresan, Sekar [49 ,50 ,51 ,52 ]
Reilly, Muredach P. [53 ]
Taylor, Kent [54 ]
Uitterlinden, Andre [3 ,4 ,34 ]
Couper, David J. [55 ]
Sitzer, Matthias [56 ]
Kahonen, Mika [18 ,57 ]
Illig, Thomas [58 ,59 ]
机构
[1] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA
[2] Univ Washington, Dept Med, Seattle, WA 98195 USA
[3] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands
[4] Sponsored Netherlands Consortium Healthy Aging NC, NGI, Rotterdam, Netherlands
[5] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA
[6] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands
[7] Ctr Med Syst Biol, Leiden, Netherlands
[8] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA
[9] Ernst Moritz Arndt Univ Greifswald, Dept Neurol, Greifswald, Germany
[10] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA
[11] Iceland Heart Assoc, Kopavogur, Iceland
[12] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA
[13] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA
[14] St Georges Univ London, Ctr Clin Neurosci, London, England
[15] Med Univ Graz, Dept Neurol, Graz, Austria
[16] Western Gen Hosp, Human Genet Unit, Inst Genet & Mol Med, MRC, Edinburgh EH4 2XU, Midlothian, Scotland
[17] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland
[18] Tampere Univ Hosp, Tampere, Finland
[19] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany
[20] Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany
[21] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
[22] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA
[23] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA
[24] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands
[25] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland
[26] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland
[27] Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany
[28] CNR, IRGB, Cagliari, Italy
[29] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany
[30] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA
[31] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA
[32] Harvard Univ, Sch Med, Boston, MA USA
[33] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[34] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands
[35] Baylor Coll Med, Houston, TX 77030 USA
[36] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Prevent, Houston, TX USA
[37] Ben Taub Gen Hosp, Houston, TX 77030 USA
[38] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel
[39] Int Comp Sci Inst, Berkeley, CA 94704 USA
[40] Med Univ Graz, Graz, Austria
[41] Gen Hosp, Dept Neurol, Graz, Austria
[42] Wellcome Trust Sanger Inst, Cambridge, England
[43] Univ Helsinki, Biomedicum, Inst Mol Med Finland, Helsinki, Finland
[44] Natl Inst Hlth & Welf, Helsinki, Finland
[45] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany
[46] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany
[47] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA
[48] Univ Iceland, Reykjavik, Iceland
[49] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
[50] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA
基金
芬兰科学院; 美国国家卫生研究院;
关键词
SINGLE NUCLEOTIDE POLYMORPHISMS; HEART-DISEASE RISK; URIC-ACID LEVELS; MYOCARDIAL-INFARCTION; GENETIC-LOCI; LIPID-LEVELS; TASK-FORCE; ATHEROSCLEROSIS; SUSCEPTIBILITY; POPULATION;
D O I
10.1038/ng.920
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 x 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.
引用
收藏
页码:940 / U40
页数:9
相关论文
共 36 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]   Association of apolipoprotein E genotypes with lipid levels and coronary risk [J].
Bennet, Anna M. ;
Di Angelantonio, Emanuele ;
Ye, Zheng ;
Wensley, Frances ;
Dahlin, Anette ;
Ahlbom, Anders ;
Keavney, Bernard ;
Collins, Rory ;
Wiman, Bjoern ;
de Faire, Ulf ;
Danesh, John .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 298 (11) :1300-1311
[3]   Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis [J].
Chasman, Daniel I. ;
Pare, Guillaume ;
Mora, Samia ;
Hopewell, Jemma C. ;
Peloso, Gina ;
Clarke, Robert ;
Cupples, L. Adrienne ;
Hamsten, Anders ;
Kathiresan, Sekar ;
Maelarstig, Anders ;
Ordovas, Jose M. ;
Ripatti, Samuli ;
Parker, Alex N. ;
Miletich, Joseph P. ;
Ridker, Paul M. .
PLOS GENETICS, 2009, 5 (11)
[4]   Genetic Loci Associated With Plasma Concentration of Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, Triglycerides, Apolipoprotein A1, and Apolipoprotein B Among 6382 White Women in Genome-Wide Analysis With Replication [J].
Chasman, Daniel I. ;
Pare, Guillaume ;
Zee, Robert Y. L. ;
Parker, Alex N. ;
Cook, Nancy R. ;
Buring, Julie E. ;
Kwiatkowski, David J. ;
Rose, Lynda M. ;
Smith, Joshua D. ;
Williams, Paul T. ;
Rieder, Mark J. ;
Rotter, Jerome I. ;
Nickerson, Deborah A. ;
Krauss, Ronald M. ;
Miletich, Joseph P. ;
Ridker, Paul M. .
CIRCULATION-CARDIOVASCULAR GENETICS, 2008, 1 (01) :21-U115
[5]   Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study [J].
Dehghan, Abbas ;
Kottgen, Anna ;
Yang, Qiong ;
Hwang, Shih Jen ;
Kao, W. H. Linda ;
Rivadeneira, Fernando ;
Boerwinkle, Eric ;
Levy, Daniel ;
Hofman, Albert ;
Astor, Brad C. ;
Benjamin, Emelia J. ;
van Duijn, Cornelia M. ;
Witteman, Jacqueline C. ;
Coresh, Josef ;
Fox, Caroline S. .
LANCET, 2008, 372 (9654) :1953-1961
[6]   Pathogenesis of atherosclerosis [J].
Falk, E .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 47 (08) :C7-C12
[7]   Genomewide linkage analysis for internal carotid artery intimal medial thickness: Evidence for linkage to chromosome 12 [J].
Fox, CS ;
Cupples, LA ;
Chazaro, I ;
Polak, JF ;
Wolf, PA ;
D'Agostino, RB ;
Ordovas, JM ;
O'Donnell, CJ .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (02) :253-261
[8]  
Greenland P, 2010, CIRCULATION, V122, pE584, DOI 10.1161/CIR.0b013e3182051b4c
[9]   The Pathology of Atherosclerosis: Plaque Development and Plaque Responses to Medical Treatment [J].
Insull, William, Jr. .
AMERICAN JOURNAL OF MEDICINE, 2009, 122 (01) :S3-S14
[10]   Carotid atherosclerosis is a stronger predictor of myocardial infarction in women than in men: A 6-year follow-up study of 6226 persons: The Tromso study [J].
Johnsen, Stein Harald ;
Mathiesen, Ellisiv B. ;
Joakimsen, Oddmund ;
Stensland, Eva ;
Wilsgaard, Tom ;
Lochen, Maja-Lisa ;
Njolstad, Inger ;
Arnesen, Egil .
STROKE, 2007, 38 (11) :2873-2880