ArticleJournal of the American College of Cardiology2019
Contribution of Gene Regulatory Networks to Heritability of Coronary Artery Disease.
Article in Journal of the American College of Cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Impact of gallstone disease on the risk of stroke and coronary artery disease: evidence from prospective observational studies and genetic analyses.BMC medicine · 2023Pooled it
- Methods for Prioritizing Causal Genes in Molecular Studies of Human Disease: The State of the Art.Genetic epidemiology · 2026Review
- A macrophage gene-regulatory network linked to clinical severity of coronary artery disease : The STARNET and NGS-PREDICT primary blood macrophage studies.Basic research in cardiology · 2025Article
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- Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques.Nature cardiovascular research · 2025Article
- Prediction of causal genes at GWAS loci with pleiotropic gene regulatory effects using sets of correlated instrumental variables.PLoS genetics · 2024Article
- Article
- Integrative gene regulatory network analysis discloses key driver genes of fibromuscular dysplasia.Nature cardiovascular research · 2024Article
- Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.Circulation research · 2024Article
- Predicting the genetic component of gene expression using gene regulatory networks.Bioinformatics advances · 2024Article
- Gene Regulatory Networks in Coronary Artery Disease.Current atherosclerosis reports · 2023Review
- Cardiovascular prevention: sometimes dreams can come true.European heart journal supplements : journal of the European Society of Cardiology · 2023Article
- Sudden death in ischemic heart disease: looking for new predictors: polygenic risk.European heart journal supplements : journal of the European Society of Cardiology · 2023Article
- Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation.Nature cardiovascular research · 2022Article
- Cardiovascular prevention: sometimes dreams can come true.European heart journal supplements : journal of the European Society of Cardiology · 2022Article
- Article
- The HDAC9-associated risk locus promotes coronary artery disease by governing TWIST1.PLoS genetics · 2022Article
- Cis-epistasis at the LPA locus and risk of cardiovascular diseases.Cardiovascular research · 2022Article
- Integrative Prioritization of Causal Genes for Coronary Artery Disease.Circulation. Genomic and precision medicine · 2022Article
- Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.Cardiovascular research · 2022Review
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Authors and funding
13 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundGenetic variants currently known to affect coronary artery disease (CAD) risk explain less than one-quarter of disease heritability. The heritability contribution of gene regulatory networks (GRNs) in CAD, which are modulated by both genetic and environmental factors, is unknown.
objectivesThis study sought to determine the heritability contributions of single nucleotide polymorphisms affecting gene expression (eSNPs) in GRNs causally linked to CAD.
methodsSeven vascular and metabolic tissues collected in 2 independent genetics-of-gene-expression studies of patients with CAD were used to identify eSNPs and to infer coexpression networks. To construct GRNs with causal relations to CAD, the prior information of eSNPs in the coexpression networks was used in a Bayesian algorithm. Narrow-sense CAD heritability conferred by the GRNs was calculated from individual-level genotype data from 9 European genome-wide association studies (GWAS) (13,612 cases, 13,758 control cases).
resultsThe authors identified and replicated 28 independent GRNs active in CAD. The genetic variation in these networks contributed to 10.0% of CAD heritability beyond the 22% attributable to risk loci identified by GWAS. GRNs in the atherosclerotic arterial wall (n = 7) and subcutaneous or visceral abdominal fat (n = 9) were most strongly implicated, jointly explaining 8.2% of CAD heritability. In all, these 28 GRNs (each contributing to >0.2% of CAD heritability) comprised 24 to 841 genes, whereof 1 to 28 genes had strong regulatory effects (key disease drivers) and harbored many relevant functions previously associated with CAD. The gene activity in these 28 GRNs also displayed strong associations with genetic and phenotypic cardiometabolic disease variations both in humans and mice, indicative of their pivotal roles as mediators of gene-environmental interactions in CAD.
conclusionsGRNs capture a major portion of genetic variance and contribute to heritability beyond that of genetic loci currently known to affect CAD risk. These networks provide a framework to identify novel risk genes/pathways and study molecular interactions within and across disease-relevant tissues leading to CAD.
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