ArticleAmerican journal of human genetics2020
Systems Genetics in Human Endothelial Cells Identifies Non-coding Variants Modifying Enhancers, Expression, and Complex Disease Traits.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Common Variants onCirculation. Heart failure · 2023Pooled it
- Multimodal atlas of human atherosclerosis links granular vascular cell states to coronary artery disease risk.medRxiv : the preprint server for health sciences · 2026Article
- An endothelial RNA splicing atlas catalogs effects of IL-1β and identifies an alternative PROCR isoform with genetic links to pleiotropic vascular disease.American journal of human genetics · 2026Article
- Multi-omics data integration from patients with carotid stenosis illuminates key molecular signatures of atherosclerotic instability.Genome medicine · 2026Article
- Functional Genomics Link REST to Endothelial Plasticity and Atherosclerosis.Circulation research · 2026Article
- Lipid raft proteomics identify endothelial myosin-9 (MYH9) as a regulator of low-density lipoprotein transcytosis and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Post-translational modification of transcription factors: perspectives in vascular medicine.Cell death & disease · 2025Review
- Coronary Artery Disease Risk Variant Dampens the Expression of CALCRL by Reducing HSF Binding to Shear Stress Responsive Enhancer in Endothelial Cells In Vitro.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
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- Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells.The Journal of cell biology · 2024Article
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- Single cell 'omic profiles of human aortic endothelial cellsbioRxiv : the preprint server for biology · 2024Article
- Review
- Multimodal CRISPR perturbations of GWAS loci associated with coronary artery disease in vascular endothelial cells.PLoS genetics · 2023Article
- Genetic Regulation of SMC Gene Expression and Splicing Predict Causal CAD Genes.Circulation research · 2023Article
- High risk oral contraceptive hormones do not directly enhance endothelial cell procoagulant activity in vitro.PloS one · 2023Article
- The use of new CRISPR tools in cardiovascular research and medicine.Nature reviews. Cardiology · 2022Review
- Single-nucleus chromatin accessibility profiling highlights regulatory mechanisms of coronary artery disease risk.Nature genetics · 2022Article
- Atherosclerosis: Recent developments.Cell · 2022Review
- Multidisciplinary approaches for elucidating genetics and molecular pathogenesis of urinary tract malformations.Kidney international · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The identification of causal variants and mechanisms underlying complex disease traits in humans is important for the progress of human disease genetics; this requires finding strategies to detect functional regulatory variants in disease-relevant cell types. To achieve this, we collected genetic and transcriptomic data from the aortic endothelial cells of up to 157 donors and four epigenomic phenotypes in up to 44 human donors representing individuals of both sexes and three major ancestries. We found thousands of expression quantitative trait loci (eQTLs) at all ranges of effect sizes not detected by the Gene-Tissue Expression Project (GTEx) in human tissues, showing that novel biological relationships unique to endothelial cells (ECs) are enriched in this dataset. Epigenetic profiling enabled discovery of over 3,000 regulatory elements whose activity is modulated by genetic variants that most frequently mutated ETS, AP-1, and NF-kB binding motifs, implicating these motifs as governors of EC regulation. Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B. Regulatory SNPs identified were enriched in coronary artery disease (CAD) loci, and this result has specific implications for PECAM-1, FES, and AXL. We also found significant roles for EC regulatory variants in modifying the traits pulse pressure, blood protein levels, and monocyte count. Lastly, we present two unlinked SNPs in the promoter of MFAP2 that exhibit pleiotropic effects on human disease traits. Together, this supports the possibility that genetic predisposition for complex disease is manifested through the endothelium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.