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

Joshua C. Bis, Maryam Kavousi, Nora Franceschini, Aaron Isaacs, Gonçalo R. Abecasis, Ulf Schminke, Wendy S. Post, Albert V. Smith, L. Adrienne Cupples, Hugh S. Markus, Reinhold Schmidt, Jennifer E. Huffman, Terho Lehtimäki, Jens Baumert, Thomas Münzel, Susan R. Heckbert, Abbas Dehghan, Kari North, Ben Oostra, Steve BevanEva Maria Stoegerer, Caroline Hayward, Olli Raitakari, Christa Meisinger, Arne Schillert, Serena Sanna, Henry Völzke, Yu Ching Cheng, Bolli Thorsson, Caroline S. Fox, Kenneth Rice, Fernando Rivadeneira, Vijay Nambi, Eran Halperin, Katja E. Petrovic, Leena Peltonen, H. Erich Wichmann, Renate B. Schnabel, Marcus Dörr, Afshin Parsa, Thor Aspelund, Serkalem Demissie, Sekar Kathiresan, Muredach P. Reilly, Kent Taylor, Andre Uitterlinden, David J. Couper, Matthias Sitzer, Mika Kähönen, Thomas Illig, Philipp S. Wild, Marco Orru, Jan Lüdemann, Alan R. Shuldiner, Gudny Eiriksdottir, Charles C. White, Jerome I. Rotter, Albert Hofman, Jochen Seissler, Tanja Zeller, Gianluca Usala, Florian Ernst, Lenore J. Launer, Ralph B. D'Agostino, Daniel H. O'Leary, Christie Ballantyne, Joachim Thiery, Andreas Ziegler, Edward G. Lakatta, Ravi Kumar Chilukoti, Tamara B. Harris, Philip A. Wolf, Bruce M. Psaty, Joseph F. Polak, Xia Li, Wolfgang Rathmann, Manuela Uda, Eric Boerwinkle, Norman Klopp, Helena Schmidt, James F. Wilson, Jorma Viikari, Wolfgang Koenig, Stefan Blankenberg, Anne B. Newman, Jacqueline Witteman, Gerardo Heiss, Cornelia Van Duijn, Angelo Scuteri, Georg Homuth, Braxton D. Mitchell, Vilmundur Gudnason, Christopher J. O'Donnell

Research output: Contribution to journalArticlepeer-review

Abstract

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 × 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.

Original languageEnglish
Pages (from-to)940-948
Number of pages9
JournalNature Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - Oct 2011

ASJC Scopus subject areas

  • Genetics

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