Abstract
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.
MeSH terms
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Adult
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Aged
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Carrier Proteins / genetics
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Cells, Cultured
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Coronary Artery Disease / genetics*
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Coronary Artery Disease / pathology
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Cytoskeletal Proteins
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Female
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Genetic Predisposition to Disease / genetics*
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Genome-Wide Association Study*
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Genotype
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Guanine Nucleotide Exchange Factors
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HEK293 Cells
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Health Information Systems*
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Insulin Resistance / genetics*
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Leukocyte Rolling / genetics
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Logistic Models
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Male
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Middle Aged
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Phenotype
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Polymorphism, Single Nucleotide
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Rho Guanine Nucleotide Exchange Factors / genetics
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Transendothelial and Transepithelial Migration / genetics*
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United Kingdom
Substances
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ARHGEF26 protein, human
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CCDC92 protein, human
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Carrier Proteins
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Cytoskeletal Proteins
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Guanine Nucleotide Exchange Factors
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Rho Guanine Nucleotide Exchange Factors