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

2017; Nature Portfolio; Volume: 49; Issue: 9 Linguagem: Inglês

10.1038/ng.3914

1546-1718

Derek Klarin, Qiuyu Zhu, Connor A. Emdin, Mark Chaffin, Steven Horner, Brian J. McMillan, Alison Leed, Michael E. Weale, Chris C. A. Spencer, François Aguet, Ayellet V. Segrè, Kristin Ardlie, Amit V. Khera, Virendar K. Kaushik, Pradeep Natarajan, Sekar Kathiresan,

Atherosclerosis and Cardiovascular Diseases

Sekar Kathiresan and colleagues perform a genome-wide association test for coronary artery disease (CAD) using data from the UK Biobank. They identify 15 new loci and perform phenome-wide association scanning, implicating insulin resistance pathways and transendothelial migration of leukocytes in CAD. UK Biobank is among the world's largest repositories for phenotypic and genotypic information in individuals of European ancestry1. 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.