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

• Published in: Nature genetics Vol. 49; no. 9; pp. 1392 - 1397
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2017; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 692/699/75/593/15; 82/80; Adult; Aged; Agriculture; Analysis; Animal Genetics and Genomics; Biomedicine; Cancer Research; Carrier Proteins - genetics; Cells, Cultured; Complications and side effects; Coronary artery; Coronary artery disease; Coronary Artery Disease - genetics; Coronary Artery Disease - pathology; Coronary heart disease; Cytoskeletal Proteins; Deoxyribonucleic acid; Development and progression; Disease control; Disease resistance; Disease susceptibility; DNA; DNA methylation; Female; Gene Function; Gene loci; Genetic analysis; Genetic aspects; Genetic Predisposition to Disease - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Guanine Nucleotide Exchange Factors; Health Information Systems; Heart diseases; HEK293 Cells; Human Genetics; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Insulin; Insulin resistance; Insulin Resistance - genetics; letter; Leukocyte migration; Leukocyte Rolling - genetics; Leukocytes; Logistic Models; Male; Middle Aged; Mutation; Nucleotide sequence; Phenotype; Polymorphism, Single Nucleotide; Repositories; Rho Guanine Nucleotide Exchange Factors - genetics; Transendothelial and Transepithelial Migration - genetics; United Kingdom; United Kingdom; United States
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3914

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 ancestry 1 . 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.