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

JC Bis, Maryam Kavousi, N Franceschini, Aaron Isaacs, GR Abecasis, U Schminke, WS Post, AV Smith, LA Cupples, HS Markus, R Schmidt, JE Huffman, T Lehtimaki, J Baumert, T Munzel, SR Heckbert, Abbas Dehghan, K North, Ben Oostra, S BevanEM Stoegerer, C Hayward, O Raitakari, C Meisinger, A Schillert, S Sanna, H Volzke, YC Cheng, B Thorsson, CS Fox, K Rice, Fernando Rivadeneira, V Nambi, E Halperin, KE Petrovic, L Peltonen, HE Wichmann, RB Schnabel, M Dorr, A Parsa, T Aspelund, S Demissie, S Kathiresan, MP Reilly, K Taylor, André Uitterlinden, DJ Couper, M Sitzer, M Kahonen, T Illig, PS Wild, M Orru, J Ludemann, AR Shuldiner, G Eiriksdottir, CC White, JI Rotter, Bert Hofman, J Seissler, T Zeller, G Usala, F Ernst, LJ (Lenore) Launer, RB D'Agostino, DH O'Leary, C Ballantyne, J Thiery, A Ziegler, EG Lakatta, RK Chilukoti, TB Harris, PA Wolf, BM Psaty, JF Polak, X Li, W Rathmann, M Uda, E Boerwinkle, N Klopp, Heléna Schmidt, JF Wilson, J Viikari, W Koenig, S Blankenberg, AB Newman, JCM Witteman, G Heiss, Cornelia Duijn, A Scuteri, G Homuth, BD Mitchell, V Gudnason, CJ O'Donnell

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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 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.
Original languageUndefined/Unknown
Pages (from-to)940-U40
JournalNature Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - 2011

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