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


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.

SUBMITTER: Bis JC 

PROVIDER: S-EPMC3257519 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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

Bis Joshua C JC   Kavousi Maryam M   Franceschini Nora N   Isaacs Aaron A   Abecasis Gonçalo R GR   Schminke Ulf U   Post Wendy S WS   Smith Albert V AV   Cupples L Adrienne LA   Markus Hugh S HS   Schmidt Reinhold R   Huffman Jennifer E JE   Lehtimäki Terho T   Baumert Jens J   Münzel Thomas T   Heckbert Susan R SR   Dehghan Abbas A   North Kari K   Oostra Ben B   Bevan Steve S   Stoegerer Eva-Maria EM   Hayward Caroline C   Raitakari Olli O   Meisinger Christa C   Schillert Arne A   Sanna Serena S   Völzke Henry H   Cheng Yu-Ching YC   Thorsson Bolli B   Fox Caroline S CS   Rice Kenneth K   Rivadeneira Fernando F   Nambi Vijay V   Halperin Eran E   Petrovic Katja E KE   Peltonen Leena L   Wichmann H Erich HE   Schnabel Renate B RB   Dörr Marcus M   Parsa Afshin A   Aspelund Thor T   Demissie Serkalem S   Kathiresan Sekar S   Reilly Muredach P MP   Taylor Kent K   Uitterlinden Andre A   Couper David J DJ   Sitzer Matthias M   Kähönen Mika M   Illig Thomas T   Wild Philipp S PS   Orru Marco M   Lüdemann Jan J   Shuldiner Alan R AR   Eiriksdottir Gudny G   White Charles C CC   Rotter Jerome I JI   Hofman Albert A   Seissler Jochen J   Zeller Tanja T   Usala Gianluca G   Ernst Florian F   Launer Lenore J LJ   D'Agostino Ralph B RB   O'Leary Daniel H DH   Ballantyne Christie C   Thiery Joachim J   Ziegler Andreas A   Lakatta Edward G EG   Chilukoti Ravi Kumar RK   Harris Tamara B TB   Wolf Philip A PA   Psaty Bruce M BM   Polak Joseph F JF   Li Xia X   Rathmann Wolfgang W   Uda Manuela M   Boerwinkle Eric E   Klopp Norman N   Schmidt Helena H   Wilson James F JF   Viikari Jorma J   Koenig Wolfgang W   Blankenberg Stefan S   Newman Anne B AB   Witteman Jacqueline J   Heiss Gerardo G   Duijn Cornelia van Cv   Scuteri Angelo A   Homuth Georg G   Mitchell Braxton D BD   Gudnason Vilmundur V   O'Donnell Christopher J CJ  

Nature genetics 20110911 10


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 ind  ...[more]

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