Abstract
AbstractPopulation-based association studies have identified many genetic risk loci for coronary artery disease (CAD), but it is often unclear how genes within these loci are linked to CAD. Here, we perform interaction proteomics for 11 CAD-risk genes to map their protein-protein interactions (PPIs) in human vascular cells and elucidate their roles in CAD. The resulting PPI networks contain interactions that are outside of known biology in the vasculature and are enriched for genes involved in immunity-related and arterial-wall-specific mechanisms. Several PPI networks derived from smooth muscle cells are significantly enriched for genetic variants associated with CAD and related vascular phenotypes. Furthermore, the networks identify 61 genes that are found in genetic loci associated with risk of CAD, prioritizing them as the causal candidates within these loci. These findings indicate that the PPI networks we have generated are a rich resource for guiding future research into the molecular pathogenesis of CAD.
Funder
Broad Institute
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
Fondation Leducq
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
Broad Institute | Stanley Center for Psychiatric Research, Broad Institute
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health
Lundbeckfonden
Novo Nordisk Fonden
Augustinus Fonden
Knud Højgaards Fond
Reinholdt W. Jorck og Hustrus Fond
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)