SynthesisArteriosclerosis, thrombosis, and vascular biology2015
Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease.
Synthesis in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed.
- Associations of genetic variation and mRNA expression of PDGF/PDGFRB pathway genes with coronary artery disease in the Chinese population.Journal of cellular and molecular medicine · 2024Article
- Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease.Annals of vascular surgery · 2024Review
- The Role of Furin and Its Therapeutic Potential in Cardiovascular Disease Risk.International journal of molecular sciences · 2024Review
- Development and Prospects of Furin Inhibitors for Therapeutic Applications.International journal of molecular sciences · 2024Review
- Functional and Multi-Omics Effects of an Optimized CRISPR-Mediated FURIN Depletion in U937 Monocytes.Cells · 2024Article
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- Genetically personalised organ-specific metabolic models in health and disease.Nature communications · 2022Article
- Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR.Metabolites · 2022Article
- Etiologic Puzzle of Coronary Artery Disease: How Important Is Genetic Component?Life (Basel, Switzerland) · 2022Review
- The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2.International journal of molecular sciences · 2022Review
- Connections for Matters of the Heart: Network Medicine in Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2022Review
- Genetic variants associated with cardiometabolic abnormalities during treatment with selective serotonin reuptake inhibitors: a genome-wide association study.The pharmacogenomics journal · 2021Article
- Article
- Downregulation of Endothelial Plexin A4 Under Inflammatory Conditions Impairs Vascular Integrity.Frontiers in cardiovascular medicine · 2021Article
- Prediction Power on Cardiovascular Disease of Neuroimmune Guidance Cues Expression by Peripheral Blood Monocytes Determined by Machine-Learning Methods.International journal of molecular sciences · 2020Article
- Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese.Frontiers in genetics · 2020Article
- Turning genome-wide association study findings into opportunities for drug repositioning.Computational and structural biotechnology journal · 2020Review
- The Integrated Landscape of Biological Candidate Causal Genes in Coronary Artery Disease.Frontiers in genetics · 2020Article
- 2018 George Lyman Duff Memorial Lecture: Genetics and Genomics of Coronary Artery Disease: A Decade of Progress.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
objectiveGenome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. APPROACHES AND
resultsUsing pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix (ECM) integrity, innate immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor), NOTCH, and the transforming growth factor-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (eg, semaphoring-regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared with random networks (P<0.001). Network centrality analysis (degree and betweenness) further identified genes (eg, NCAM1, FYN, FURIN, etc) likely to play critical roles in the maintenance and functioning of several of the replicated pathways.
conclusionsThese findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD.
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