2016
DOI: 10.1161/atvbaha.115.306725
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Network-Based Identification and Prioritization of Key Regulators of Coronary Artery Disease Loci

Abstract: Objective Recent genome-wide association studies of coronary artery disease (CAD) have revealed 58 genome-wide significant and 148 suggestive genetic loci. However, the molecular mechanisms through which they contribute to CAD and the clinical implications of these findings remain largely unknown. We aim to retrieve gene subnetworks of the 206 CAD loci and identify and prioritize candidate regulators to better understand the biological mechanisms underlying the genetic associations. Approach and Results We d… Show more

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Cited by 63 publications
(51 citation statements)
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“…The extension of genes increases the probability of including false positive genes, but offers a better opportunity to infer biological mechanisms and pathways contributing to CAD (Zhao et al, 2016). …”
Section: Human Genome-wide Association Results: Overlap With Mouse Stmentioning
confidence: 99%
See 2 more Smart Citations
“…The extension of genes increases the probability of including false positive genes, but offers a better opportunity to infer biological mechanisms and pathways contributing to CAD (Zhao et al, 2016). …”
Section: Human Genome-wide Association Results: Overlap With Mouse Stmentioning
confidence: 99%
“…Three separate studies have modeled CAD pathways based on data of the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Consortium (CARDIoGRAM) (Ghosh et al, 2015b; Makinen et al, 2014; Zhao et al, 2016). Mäkinen et al utilized a SNP set enrichment analysis (SSEA) that first mapped CARDIoGRAM GWAS to genes based on expression quantitative trait loci (eQTLs), and then assessed the enrichment of CAD signals in tissue-specific co-expression networks and canonical pathways from Biocarta, KEGG and Reactome databases.…”
Section: Pathway Modeling: Concordance Of Human and Mouse Studiesmentioning
confidence: 99%
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“…These new resources and techniques have already provided important mechanistic insights for several novel susceptibility loci for CAD, including those regions harboring the genes CDKN2B, SORT1, TCF21, ADAMTS7, SMAD3, and other loci (165)(166)(167)(168)(169)(170)(171)(172). Although this understanding has not yet been translated to therapeutic agents targeting these loci, the rapid path of translation for other susceptibility loci, such as PCSCK9, provides some reassurance that such developments are forthcoming and are likely to provide us with groundbreaking opportunities to further reduce, and possibility eliminate, the threat of CAD in the 21 st century.…”
Section: Future Directionsmentioning
confidence: 99%
“…The results that have been reported include in vitro assays, ex vivo assays, in vivo assays using animal models, in vivo assays in humans, clinical trials, cell biology, molecular biology and, more recently, genome-wide assays at the level of transcriptomics [131], proteomics [132], metabolomics [133], as well as their multi-omics integration and in silico predictions via modeling approaches [134]. This systems biology approach has been applied to help unravel the pathological mechanisms in human diseases, such as Alzheimer's [135], coronary artery disease [136], cardiovascular disease, type 2 diabetes [137] and cancer [138], among others. We believe that a similar approach will prove extremely useful to better understand the pathogenesis of psoriasis, making it easier to find new therapeutic strategies for this disease.…”
Section: Discussionmentioning
confidence: 99%