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Nat Genet DOI:10.1038/ng.3914

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

Publication TypeJournal Article
Year of Publication2017
AuthorsKlarin, D, Zhu, QMartin, 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, Kathiresan, S
Corporate AuthorsCARDIOGRAMplusC4D Consortium
JournalNat Genet
Date Published2017 Sep
KeywordsAdult, Aged, Carrier Proteins, Cells, Cultured, Coronary Artery Disease, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Health Information Systems, HEK293 Cells, Human Umbilical Vein Endothelial Cells, Humans, Insulin Resistance, Leukocyte Rolling, Logistic Models, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Rho Guanine Nucleotide Exchange Factors, Transendothelial and Transepithelial Migration, United Kingdom

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.


Alternate JournalNat. Genet.
PubMed ID28714974
PubMed Central IDPMC5577383
Grant ListKL2 TR001100 / TR / NCATS NIH HHS / United States
MC_QA137853 / / Medical Research Council / United Kingdom
R01 HL127564 / HL / NHLBI NIH HHS / United States
T32 HL007734 / HL / NHLBI NIH HHS / United States