ArticleGenome biology2020
Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Therapeutic Target Mapping to Advance Drug Repurposing for Cardiovascular Disease: A Perspective from an Explanted Heart Biobank.Journal of personalized medicine · 2026Review
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Vascular smooth muscle cell state trajectories mediate molecular mechanisms of coronary disease risk.Nature communications · 2026Article
- Cell type-specific epigenetic regulatory circuitry of coronary artery disease loci.Nature communications · 2026Article
- Integrative functional genomics analysis identifies pleiotropic genes for vascular diseases.Nature communications · 2026Article
- The inner nuclear membrane protein LEMD3 organizes the 3D chromatin architecture to maintain vascular smooth muscle cell identity.Nature communications · 2025Article
- Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Identifying genetic variants associated with chromatin looping and genome function.Nature communications · 2024Article
- Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity.Cell genomics · 2024Article
- COLOCdb: a comprehensive resource for multi-model colocalization of complex traits.Nucleic acids research · 2024Article
- Leveraging molecular quantitative trait loci to comprehend complex diseases/traits from the omics perspective.Human genetics · 2023Review
- Comorbidity genetic risk and pathways impact SARS-CoV-2 infection outcomes.Scientific reports · 2023Article
- A global high-density chromatin interaction network reveals functional long-range and trans-chromosomal relationships.Genome biology · 2022Article
- Single-nucleus chromatin accessibility profiling highlights regulatory mechanisms of coronary artery disease risk.Nature genetics · 2022Article
- Article
- Transcription factor regulation of eQTL activity across individuals and tissues.PLoS genetics · 2022Article
- Multi-Omics Approaches to Define Calcific Aortic Valve Disease Pathogenesis.Circulation research · 2021Review
- Emerging Role of Long Non-Coding RNAs in Diabetic Vascular Complications.Frontiers in endocrinology · 2021Review
- Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping.Genome biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTo investigate the epigenetic and transcriptional mechanisms of coronary artery disease (CAD) risk, as well as the functional regulation of chromatin structure and function, we create a catalog of genetic variants associated with three stages of transcriptional cis-regulation in primary human coronary artery vascular smooth muscle cells (HCASMCs).
resultsWe use a pooling approach with HCASMC lines to map regulatory variants that mediate binding of the CAD-associated transcription factor TCF21 with ChIPseq studies (bQTLs), variants that regulate chromatin accessibility with ATACseq studies (caQTLs), and chromosomal looping with Hi-C methods (clQTLs). We examine the overlap of these QTLs and their relationship to smooth muscle-specific genes and transcription factors. Further, we use multiple analyses to show that these QTLs are highly associated with CAD GWAS loci and correlate to lead SNPs where they show allelic effects. By utilizing genome editing, we verify that identified functional variants can regulate both chromatin accessibility and chromosomal looping, providing new insights into functional mechanisms regulating chromatin state and chromosomal structure. Finally, we directly link the disease-associated TGFB1-SMAD3 pathway to the CAD-associated FN1 gene through a response QTL that modulates both chromatin accessibility and chromosomal looping.
conclusionsTogether, these studies represent the most thorough mapping of multiple QTL types in a highly disease-relevant primary cultured cell type and provide novel insights into their functional overlap and mechanisms that underlie these genomic features and their relationship to disease risk.
Indexed as
Identifiers
What OpenQuestion holds
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.