2018
DOI: 10.1038/s41598-018-20721-6
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Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets

Abstract: Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these loci are largely unknown and an untapped resource to improve our understanding of CAD pathophysiology and identify potential therapeutic targets. Here, we prioritized 68 genes as the most likely causal genes at genome-wide significant loci identified by GWAS of CAD and examined their regulatory roles in 286 metabolic and vascular t… Show more

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Cited by 45 publications
(54 citation statements)
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References 82 publications
(73 reference statements)
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“…Previous GWASs have identified potential biological pathways underlying the associations between genetic loci and CAD ( 75 , 76 ). Network analysis of functional gene-gene interactions may be informative with regard to the clarification of biological processes underlying CAD and to the identification of therapeutic targets for this condition ( 77 ). Therefore the present study performed GO and network analyses to predict biological processes associated with the identified genes, and the interactions between these genes and those previously shown to be associated with MI, hypertension, or CKD.…”
Section: Discussionmentioning
confidence: 99%
“…Previous GWASs have identified potential biological pathways underlying the associations between genetic loci and CAD ( 75 , 76 ). Network analysis of functional gene-gene interactions may be informative with regard to the clarification of biological processes underlying CAD and to the identification of therapeutic targets for this condition ( 77 ). Therefore the present study performed GO and network analyses to predict biological processes associated with the identified genes, and the interactions between these genes and those previously shown to be associated with MI, hypertension, or CKD.…”
Section: Discussionmentioning
confidence: 99%
“…A recent study 30 of CAD prioritized 184 candidate genes as the most likely causal genes for CAD based on functional evidence. These genes were involved in 286 modules.…”
Section: Resultsmentioning
confidence: 99%
“…Recent GWASs have identified potential biological pathways underlying the association between genetic loci and CAD, including metabolism of LDL-cholesterol, triglycerides and lipoprotein (a); insulin resistance; thrombosis; inflammation, cell adhesion and transendothelial migration; cellular proliferation, vascular remodeling and extracellular matrix metabolism; and vascular tone and nitric oxide signaling ( 50 , 51 ). Network analysis of functional gene-gene interactions may be informative to clarify biological process of CAD and to identify therapeutic targets for this condition ( 52 ). Therefore, the present study performed gene ontology and network analyses to predict biological processes of the identified genes and interactions between these genes and those previously revealed to be associated with CAD.…”
Section: Discussionmentioning
confidence: 99%