Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.
Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.
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全基因组关联研究，用于冠状动脉钙化，随访心肌梗塞。
DOI：
10.1161/circulationaha.110.974899
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发表时间：
2011-12-20
期刊：
影响因子：
37.8
通讯作者：
Witteman JC
中科院分区：
文献类型：
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作者：
O'Donnell CJ;Kavousi M;Smith AV;Kardia SL;Feitosa MF;Hwang SJ;Sun YV;Province MA;Aspelund T;Dehghan A;Hoffmann U;Bielak LF;Zhang Q;Eiriksdottir G;van Duijn CM;Fox CS;de Andrade M;Kraja AT;Sigurdsson S;Elias-Smale SE;Murabito JM;Launer LJ;van der Lugt A;Kathiresan S;CARDIoGRAM Consortium;Krestin GP;Herrington DM;Howard TD;Liu Y;Post W;Mitchell BD;O'Connell JR;Shen H;Shuldiner AR;Altshuler D;Elosua R;Salomaa V;Schwartz SM;Siscovick DS;Voight BF;Bis JC;Glazer NL;Psaty BM;Boerwinkle E;Heiss G;Blankenberg S;Zeller T;Wild PS;Schnabel RB;Schillert A;Ziegler A;Münzel TF;White CC;Rotter JI;Nalls M;Oudkerk M;Johnson AD;Newman AB;Uitterlinden AG;Massaro JM;Cunningham J;Harris TB;Hofman A;Peyser PA;Borecki IB;Cupples LA;Gudnason V;Witteman JC
冠状动脉钙化（CAC）是冠状动脉粥样硬化的一种非侵入性测量方法，是大多数心肌梗死（MI）病例的基础。我们的目的是确定与CAC相关的常见遗传变异，并进一步研究它们与MI的相关性。计算机断层扫描用于评估CAC的量。CAC全基因组关联研究的荟萃分析在来自5个独立社区队列的9，961名男性和女性中进行，并在另外3个独立队列（n= 6，032）中重复。我们在多个大的MI全基因组关联研究中检测了与CAC数量相关的单核苷酸多态性（SNP）与MI的关联。染色体9 p21上靠近CDKN 2A和CDKN 2B的SNP（最高SNP：rs 1333049，P=7.58×10−19）和6p 24（最高SNP：rs 9349379，在PHACTR 1基因内，P=2.65×10−11）与CAC和MI的CAC具有全基因组显著相关性。此外，有证据表明SNP与CAC和MI在许多其他基因座（包括3q 22（MRAS基因），13 q34（COL 4A 1/COL 4A 2基因）和1 p13（SORT 1基因））的一致性。9 p21和PHACTR 1基因位点的SNPs与CAC和MI密切相关，其他位点的SNPs也与CAC和MI密切相关。多个基因位点与潜在冠状动脉粥样硬化和临床事件的发生相关。
Coronary artery calcification (CAC) detected by computed tomography is a non-invasive measure of coronary atherosclerosis, that underlies most cases of myocardial infarction (MI). We aimed to identify common genetic variants associated with CAC and further investigate their associations with MI. Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was carried out in 9,961 men and women from five independent community-based cohorts, with replication in three additional independent cohorts (n=6,032). 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 with MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). 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.