英国生物银行的基因分析将胰岛素抵抗和跨内皮迁移途径与冠状动脉疾病联系起来。
Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease.
作者信息
Klarin Derek, Zhu Qiuyu Martin, Emdin Connor A, Chaffin Mark, Horner Steven, McMillan Brian J, Leed Alison, Weale Michael E, Spencer Chris C A, Aguet François, Segrè Ayellet V, Ardlie Kristin G, Khera Amit V, Kaushik Virendar K, Natarajan Pradeep, Kathiresan Sekar
机构信息
Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
出版信息
Nat Genet. 2017 Sep;49(9):1392-1397. doi: 10.1038/ng.3914. Epub 2017 Jul 17.
UK Biobank is among the world's largest repositories for phenotypic and genotypic information in individuals of European ancestry. We performed a genome-wide association study in UK Biobank testing ∼9 million DNA sequence variants for association with coronary artery disease (4,831 cases and 115,455 controls) and carried out meta-analysis with previously published results. We identified 15 new loci, bringing the total number of loci associated with coronary artery disease to 95 at the time of analysis. Phenome-wide association scanning showed that CCDC92 likely affects coronary artery disease through insulin resistance pathways, whereas experimental analysis suggests that ARHGEF26 influences the transendothelial migration of leukocytes.
英国生物银行是世界上最大的欧洲血统个体表型和基因型信息储存库之一。我们在英国生物银行进行了一项全基因组关联研究，检测了约900万个DNA序列变异与冠状动脉疾病（4831例病例和115455例对照）的关联，并与先前发表的结果进行了荟萃分析。我们确定了15个新位点，在分析时使与冠状动脉疾病相关的位点总数达到95个。全表型组关联扫描显示，CCDC92可能通过胰岛素抵抗途径影响冠状动脉疾病，而实验分析表明，ARHGEF26影响白细胞的跨内皮迁移。
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