Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease.

Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease.
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英国生物库中的遗传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。

DOI:
10.1038/ng.3914
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发表时间:
2017-09
期刊:
影响因子:
30.8
通讯作者:
Kathiresan S
Kathiresan S
中科院分区:
生物学1区
文献类型:
--
作者:
Klarin D;Zhu QM;Emdin CA;Chaffin M;Horner S;McMillan BJ;Leed A;Weale ME;Spencer CCA;Aguet F;Segrè AV;Ardlie KG;Khera AV;Kaushik VK;Natarajan P;CARDIoGRAMplusC4D Consortium;Kathiresan S

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英国生物库是世界上最大的欧洲血统个体表型和基因信息储存库之一。我们在英国生物库中进行了一项全基因组相关性研究,测试了约900万个与冠状动脉疾病相关的DNA序列变异(4831例;115,455名对照),并与之前发表的结果进行了荟萃分析。我们确定了15个新的基因座,使冠状动脉疾病相关基因座的总数达到95个。全基因组联合扫描显示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细胞迁移。
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; 115,455 controls) and carried out meta-analysis with previously published results. We identified fifteen novel loci, bringing the total number of coronary artery disease-associated loci to 95. Phenome-wide association scanning revealed that CCDC92 likely affects coronary artery disease through insulin resistance pathways whereas experimental analysis suggests that ARHGEF26 impacts the transendothelial migration of leukocytes.
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