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

Nat Genet

Authors	Derek Klarin Qiuyu Zhu Connor Emdin Mark Chaffin Steven Horner Brian McMillan Alison Leed Michael Weale Chris Spencer Francois Aguet Ayellet Segrè Kristin Ardlie Amit Khera Virendar Kaushik Pradeep Natarajan CARDIOGRAMplusC4D Consortium Sekar Kathiresan
Keywords	Female Humans Male Adult Aged Genetic Predisposition to Disease Phenotype Genotype Middle Aged Carrier Proteins Genome-Wide Association Study Polymorphism, Single Nucleotide HEK293 Cells Cells, Cultured Health Information Systems Coronary Artery Disease Insulin Resistance Logistic Models United Kingdom Human Umbilical Vein Endothelial Cells Leukocyte Rolling Rho Guanine Nucleotide Exchange Factors Transendothelial and Transepithelial Migration
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.
Year of Publication	2017
Journal	Nat Genet
Volume	49
Issue	9
Pages	1392-1397
Date Published	2017 Sep
ISSN	1546-1718
DOI	10.1038/ng.3914
PubMed ID	28714974
PubMed Central ID	PMC5577383
Links
Grant list	KL2 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