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Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.


ABSTRACT: BACKGROUND:Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS:Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS:SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

SUBMITTER: O'Donnell CJ 

PROVIDER: S-EPMC3397173 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.

O'Donnell Christopher J CJ   Kavousi Maryam M   Smith Albert V AV   Kardia Sharon L R SL   Feitosa Mary F MF   Hwang Shih-Jen SJ   Sun Yan V YV   Province Michael A MA   Aspelund Thor T   Dehghan Abbas A   Hoffmann Udo U   Bielak Lawrence F LF   Zhang Qunyuan Q   Eiriksdottir Gudny G   van Duijn Cornelia M CM   Fox Caroline S CS   de Andrade Mariza M   Kraja Aldi T AT   Sigurdsson Sigurdur S   Elias-Smale Suzette E SE   Murabito Joanne M JM   Launer Lenore J LJ   van der Lugt Aad A   Kathiresan Sekar S   Krestin Gabriel P GP   Herrington David M DM   Howard Timothy D TD   Liu Yongmei Y   Post Wendy W   Mitchell Braxton D BD   O'Connell Jeffrey R JR   Shen Haiqing H   Shuldiner Alan R AR   Altshuler David D   Elosua Roberto R   Salomaa Veikko V   Schwartz Stephen M SM   Siscovick David S DS   Voight Benjamin F BF   Bis Joshua C JC   Glazer Nicole L NL   Psaty Bruce M BM   Boerwinkle Eric E   Heiss Gerardo G   Blankenberg Stefan S   Zeller Tanja T   Wild Philipp S PS   Schnabel Renate B RB   Schillert Arne A   Ziegler Andreas A   Münzel Thomas F TF   White Charles C CC   Rotter Jerome I JI   Nalls Michael M   Oudkerk Matthijs M   Johnson Andrew D AD   Newman Anne B AB   Uitterlinden Andre G AG   Massaro Joseph M JM   Cunningham Julie J   Harris Tamara B TB   Hofman Albert A   Peyser Patricia A PA   Borecki Ingrid B IB   Cupples L Adrienne LA   Gudnason Vilmundur V   Witteman Jacqueline C M JC  

Circulation 20111205 25


<h4>Background</h4>Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI.<h4>Methods and results</h4>Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from  ...[more]

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