Thirty-five common variants for coronary artery disease: the fruits of much collaborative labour.
Thirty-five common variants for coronary artery disease: the fruits of much collaborative labour.
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DOI：
10.1093/hmg/ddr384
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发表时间：
2011-10-15
影响因子：
3.5
通讯作者：
Farrall M
中科院分区：
文献类型：
--
作者：
Peden JF;Farrall M
冠状动脉疾病（CAD）是全球范围内的主要死亡原因。受影响的个人聚集在家庭中的模式，反映了许多易感基因的共享。涉及数万例病例和对照的全基因组和大规模基因中心基因分型研究现已将常见疾病变异定位于34个不同的基因座。一些冠心病常见变异表现出等位基因异质性或拷贝数变异。一些基因座包括候选基因，其暗示疾病发病机制的常规或新兴风险因子介导的机制。数量性状基因座与危险因素的关联在孟德尔随机化研究以及致病变异的精细定位中提供了信息。但是，对于大多数基因座，合理的机制联系是不确定的或模糊的，目前，但提供了潜在的新方向研究这种疾病的发病机制。常见变异解释了疾病风险个体间变异的0.4%，不超过冠状动脉疾病总遗传率的13%。尽管许多CAD基因目前尚未发现，但更大规模的全基因组关联研究可能会绘制出更多常见/低突变率变异，并希望在医学重测序实验中也能识别出低频率或罕见的高突变率变异。
Coronary artery disease (CAD) is the leading cause of death worldwide. Affected individuals cluster in families in patterns that reflect the sharing of numerous susceptibility genes. Genome-wide and large-scale gene-centric genotyping studies that involve tens of thousands of cases and controls have now mapped common disease variants to 34 distinct loci. Some coronary disease common variants show allelic heterogeneity or copy number variation. Some of the loci include candidate genes that imply conventional or emerging risk factor-mediated mechanisms of disease pathogenesis. Quantitative trait loci associations with risk factors have been informative in Mendelian randomization studies as well as fine-mapping of causative variants. But, for most loci, plausible mechanistic links are uncertain or obscure at present but provide potentially novel directions for research into this disease's pathogenesis. The common variants explain ∼4% of inter-individual variation in disease risk and no more than 13% of the total heritability of coronary disease. Although many CAD genes are presently undiscovered, it is likely that larger collaborative genome-wide association studies will map further common/low-penetrance variants and hoped that low-frequency or rare high-penetrance variants will also be identified in medical resequencing experiments.
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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：
29
作者：
Kjolby, Mads;Andersen, Olav M.;Nykjaer, Anders
通讯作者：
Nykjaer, Anders
影响因子：
30.8
作者：
Levy, Daniel;Ehret, Georg B.;Rice, Kenneth;Verwoert, Germaine C.;Launer, Lenore J.;Dehghan, Abbas;Glazer, Nicole L.;Morrison, Alanna C.;Johnson, Andrew D.;Aspelund, Thor;Aulchenko, Yurii;Lumley, Thomas;Koettgen, Anna;Vasan, Ramachandran S.;Rivadeneira, Fernando;Eiriksdottir, Gudny;Guo, Xiuqing;Arking, Dan E.;Mitchell, Gary F.;Mattace-Raso, Francesco U. S.;Smith, Albert V.;Taylor, Kent;Scharpf, Robert B.;Hwang, Shih-Jen;Sijbrands, Eric J. G.;Bis, Joshua;Harris, Tamara B.;Ganesh, Santhi K.;O'Donnell, Christopher J.;Hofman, Albert;Rotter, Jerome I.;Coresh, Josef;Benjamin, Emelia J.;Uitterlinden, Andre G.;Heiss, Gerardo;Fox, Caroline S.;Witteman, Jacqueline C. M.;Boerwinkle, Eric;Wang, Thomas J.;Gudnason, Vilmundur;Larson, Martin G.;Chakravarti, Aravinda;Psaty, Bruce M.;van Duijn, Cornelia M.
通讯作者：
van Duijn, Cornelia M.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Broadbent, Helen M.;Peden, John F.;Watkins, Hugh
通讯作者：
Watkins, Hugh