ArticleNature2011
9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 340 papers, 6 of them syntheses that pooled it.
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.
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
340 citing papers in PubMed, 6 syntheses or guidelines pooled it, 621 citations in OpenAlex.
- Variant effect predictors: a systematic review and practical guide.Human genetics · 2024Pooled it
- Genetic association between CDKN2B-AS1 polymorphisms and the susceptibility of primary open-angle glaucoma (POAG): a meta-analysis from 21,775 subjects.Irish journal of medical science · 2022Pooled it
- Effect of 9p21.3 (lncRNA and CDKN2A/2B) variant on lipid profile.Frontiers in cardiovascular medicine · 2022Pooled it
- KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.JCI insight · 2019Pooled it
- Association between long non-coding RNA polymorphisms and cancer risk: a meta-analysis.Bioscience reports · 2018Pooled it
- Association of CDKN2BAS polymorphism rs4977574 with coronary heart disease: a case-control study and a meta-analysis.International journal of molecular sciences · 2014Pooled it
- Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus.Scientific reports · 2019Trial
- Long Non-coding RNAs Genes Polymorphisms and Their Expression Levels in Patients With Rheumatoid Arthritis.Frontiers in immunology · 2019Trial
- Trial
- Circulating "LncPPARδ" From Monocytes as a Novel Biomarker for Coronary Artery Diseases.Medicine · 2016Trial
- ANRIL in Cardiovascular Diseases: Expression, Mechanism and Therapeutic Implications.Cardiovascular drugs and therapy · 2026Review
- Chromatin topology and distal elements underlie divergent cell-type-specific regulation of 9p21 locus cell cycle genes.Cell genomics · 2026Article
- Association between neuroticism, genetic susceptibility, and peripheral artery disease risk: a prospective study in UK Biobank.European archives of psychiatry and clinical neuroscience · 2026Article
- Senescence-associated and immune-related 9p21.3 locus genes in colorectal cancer: epigenetic architecture, molecular landscape and therapeutic possibilities.Frontiers in cell and developmental biology · 2026Review
- Role of ncRNAs in Neurological Disorders and Cardiovascular Diseases.Experientia supplementum (2012) · 2026Review
- ThebioRxiv : the preprint server for biology · 2025Article
- Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Myocardial infarction activates the 9p21.3 orthologous locus expression, but its absence does not alter cardiac pathophysiology in ischemia.Physiological reports · 2025Article
- Multiomics Analysis of a Micronutrient-Rich Dietary Pattern and the Aging Genotype 9p21 on the Plasma Proteome of Young Adults.Nutrients · 2025Article
- Associations of Blood Lipid-Related Polygenic Scores, Lifestyle Factors and Their Combined Effects with Risk of Coronary Artery Disease in the UK Biobank Cohort.Journal of cardiovascular translational research · 2025Article
280 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the 9p21 gene desert associated with coronary artery disease (CAD) and type 2 diabetes. Despite evidence for a role of the associated interval in neighbouring gene regulation, the biological underpinnings of these genetic associations with CAD or type 2 diabetes have not yet been explained. Here we identify 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and six times denser than the whole genome (P < 6.55 × 10(-33)). The CAD risk alleles of SNPs rs10811656 and rs10757278 are located in one of these enhancers and disrupt a binding site for STAT1. Lymphoblastoid cell lines homozygous for the CAD risk haplotype show no binding of STAT1, and in lymphoblastoid cell lines homozygous for the CAD non-risk haplotype, binding of STAT1 inhibits CDKN2BAS (also known as CDKN2B-AS1) expression, which is reversed by short interfering RNA knockdown of STAT1. Using a new, open-ended approach to detect long-distance interactions, we find that in human vascular endothelial cells the enhancer interval containing the CAD locus physically interacts with the CDKN2A/B locus, the MTAP gene and an interval downstream of IFNA21. In human vascular endothelial cells, interferon-γ activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus, including STAT1-binding, long-range enhancer interactions and altered expression of neighbouring genes. Our findings establish a link between CAD genetic susceptibility and the response to inflammatory signalling in a vascular cell type and thus demonstrate the utility of genome-wide association study findings in directing studies to novel genomic loci and biological processes important for disease aetiology.
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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.