Large scale association analysis identifies three susceptibility loci for coronary artery disease.
Large scale association analysis identifies three susceptibility loci for coronary artery disease.
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DOI：
10.1371/journal.pone.0029427
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
FGENTCARD consortium
中科院分区：
文献类型：
--
作者：
Saade S;Cazier JB;Ghassibe-Sabbagh M;Youhanna S;Badro DA;Kamatani Y;Hager J;Yeretzian JS;El-Khazen G;Haber M;Salloum AK;Douaihy B;Othman R;Shasha N;Kabbani S;Bayeh HE;Chammas E;Farrall M;Gauguier D;Platt DE;Zalloua PA;FGENTCARD consortium
全基因组关联研究 (GWAS) 及其将 DNA 变异与心肌梗塞 (MI) 和/或冠状动脉疾病 (CAD) 相关的重复研究主要基于欧洲或东亚血统的人群。在具有独特遗传背景和生活方式的多个人群中复制最显着相关的多态性对于理解 CAD 等多因素疾病的病理生理学至关重要。我们利用黎巴嫩队列对先前确定的 9 个 CAD/MI 易感位点（LTA、CDKN2A-CDKN2B、CELSR2-PSRC1-SORT1、CXCL12、MTHFD1L、WDR12、PCSK9、SH2B3 和 SLC22A3）以及相关表型中的 88 个基因进行了复制研究。该研究对 2,002 名患者进行了详细的人口统计、临床特征和心导管检查结果。 MTHFD1L 中的一种标记物 rs6922269 对 MI 具有显着保护作用（OR = 0.68，p = 0.0035），而 CDKN2A-CDKN2B 中的变体 rs4977574 与 MI 显着相关（OR = 1.33，p = 0.0086）。在调整 CAD 家族史、性别、高血压、高脂血症、糖尿病和吸烟后，发现了相关性。对先前发表的 88 个相关表型基因的平行研究涵盖 20,225 个标记，其中四分之三具有估算基因型。该研究基于我们的全基因组基因型数据集，使用 HapMap CEU 群体作为参考，将整个基因组估算到 HapMap II 版本 22。对覆盖所选基因的 88 个区域的基因分型和推算变异进行了分析。该方法复制了 HNRNPA3P1-CXCL12 与 CAD 的关联，并确定了 CDKAL1、ST6GAL1 和 PTPRD 与 CAD 的新的显着关联。我们的研究为 CAD/MI 多因素方面的重要性提供了证据，并描述了导致其病因的基因。
Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
8.2
作者：
Below, J. E.;Gamazon, E. R.;Morrison, J. V.;Konkashbaev, A.;Pluzhnikov, A.;McKeigue, P. M.;Parra, E. J.;Elbein, S. C.;Hallman, D. M.;Nicolae, D. L.;Bell, G. I.;Cruz, M.;Cox, N. J.;Hanis, C. L.
通讯作者：
Hanis, C. L.
DOI：
10.1083/jcb.200501141
发表时间：
2005-08-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hölzel M;Rohrmoser M;Schlee M;Grimm T;Harasim T;Malamoussi A;Gruber-Eber A;Kremmer E;Hiddemann W;Bornkamm GW;Eick D
通讯作者：
Eick D
与人类血液低密度脂蛋白胆固醇、高密度脂蛋白胆固醇或甘油三酯相关的六个新位点。
影响因子：
30.8
作者：
Kathiresan, Sekar;Melander, Olle;Guiducci, Candace;Surti, Aarti;Burtt, Noel P.;Rieder, Mark J.;Cooper, Gregory M.;Roos, Charlotta;Voight, Benjamin F.;Havulinna, Aki S.;Wahlstrand, Bjorn;Hedner, Thomas;Corella, Dolores;Tai, E. Shyong;Ordovas, Jose M.;Berglund, Goran;Vartiainen, Erkki;Jousilahti, Pekka;Hedblad, Bo;Taskinen, Marja-Riitta;Newton-Cheh, Christopher;Salomaa, Veikko;Peltonen, Leena;Groop, Leif;Altshuler, David M.;Orho-Melander, Marju
通讯作者：
Orho-Melander, Marju
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari