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

Nat Genet. 2017 Sep;49(9):1392-1397. doi: 10.1038/ng.3914. Epub 2017 Jul 17.

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

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

Substances

  • ARHGEF26 protein, human
  • CCDC92 protein, human
  • Carrier Proteins
  • Rho Guanine Nucleotide Exchange Factors