Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA295524 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2378590_1.fastq.gz | Fastqsanger.gz | |||
| SRR2378590_2.fastq.gz | Fastqsanger.gz | |||
| SRR2378600_1.fastq.gz | Fastqsanger.gz | |||
| SRR2378600_2.fastq.gz | Fastqsanger.gz | |||
| SRR2378591_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 42 |
Similar Datasets
Project description:Coronary artery disease (CAD) is the leading cause of mortality and morbidity driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with CAD and myocardial infarction (MI) susceptibility in multi-ethnic populations. The majority of these variants reside in non-coding regulatory regions and are co-inherited with hundreds of candidate regulatory SNPs. Herein, we use integrative genomic, epigenomic, and transcriptomic fine-mapping in human coronary artery smooth muscle cells (HCASMC) and tissues to identify causal regulatory variation and mechanisms responsible for CAD associations. Using these genome-wide maps we prioritize 65 candidate variants and perform allele-specific binding and expression analyses on 7 top candidates. We validate our findings in two independent cohorts of diseased human arterial expression quantitative trait loci (eQTL), which together demonstrate fundamental links between CAD associations and regulatory function in the appropriate disease context.
2016-07-06 | GSE72696 | GEO
Project description:Coronary artery disease (CAD) is the leading cause of mortality and morbidity driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with CAD and myocardial infarction (MI) susceptibility in multi-ethnic populations. The majority of these variants reside in non-coding regulatory regions and are co-inherited with hundreds of candidate regulatory SNPs. Herein, we use integrative genomic, epigenomic, and transcriptomic fine-mapping in human coronary artery smooth muscle cells (HCASMC) and tissues to identify causal regulatory variation and mechanisms responsible for CAD associations. Using these genome-wide maps we prioritize 65 candidate variants and perform allele-specific binding and expression analyses on 7 top candidates. We validate our findings in two independent cohorts of diseased human arterial expression quantitative trait loci (eQTL), which together demonstrate fundamental links between CAD associations and regulatory function in the appropriate disease context. We performed ATAC-seq, ChIP-seq, and RNA-seq on human coronary artery smooth muscle cells grown in SmGM-2 Smooth Muscle Growth Medium-2 including hEGF, insulin, hFGF-B and FBS, but without antibiotics (Lonza, #CC-3182). For ATAC-seq and RNA-seq we performed stimulations with growth factors (TGF-B1, PDGF-BB, PDGF-DD) versus serum-free control. We conducted two biological replicates for each condition using independent donors. For ATAC-seq experiments, sequencing was completed on an Illumina Hiseq 2500, paired-end 50bp reads. For ChIP-seq we performed immunoprecipitations using H3K27ac (Abcam ab4729). We conducted two biological replicates using HCASMC from independent donors, and also did an IgG control for these studies. For RNA-seq we also conducted two replicates using HCASMC from independent donors. For both ChIP-seq and RNA-seq experiments, sequencing was completed on an Illumina HiSeq 2500, paired-end 100bp reads. We also performed ex-vivo ATAC-seq on frozen tissues (isolated media) from normal and atherosclerotic human coronary arteries, using three independent donors for each. Sequencing was also completed on an Illumina HiSeq 2500, paired end 50bp reads.
2016-07-06 | E-GEOD-72696 | biostudies-arrayexpress
Project description:Genome-wide association studies (GWAS) have identified hundreds of loci associated with vascular diseases such as coronary artery disease (CAD) and myocardial infarction (MI), and hypertension. However, the biological roles for many of these loci enriched in the vessel wall remains unknown. Among these, UFL1-FHL5 (chr6q16.1) emerged as a genome-wide significant locus in a recent CAD/MI meta-analysis. Here, we use an integrative approach leveraging human genetics, epigenomic profiling, and in vitro functional and ex vivo imaging analyses to prioritize FHL5 as the top candidate causal gene and reveal the molecular mechanisms of its pleiotropic genetic associations. Notably, FHL5 overexpression in coronary artery smooth muscle cells (SMC) increased vascular calcification and dysregulated processes related to extracellular matrix organization and calcium handling. Lastly, by mapping FHL5 binding sites genome-wide using CUT&RUN, we identified regulatory interactions with downstream disease loci having putative roles in SMC phenotypic modulation. Together, these trans-acting mechanisms may account for a portion of the heritable risk for CAD/MI and other complex vascular diseases.
2022-10-31 | GSE201571 | GEO
Project description:Genome-wide association studies (GWAS) have identified hundreds of loci associated with vascular diseases such as coronary artery disease (CAD) and myocardial infarction (MI), and hypertension. However, the biological roles for many of these loci enriched in the vessel wall remains unknown. Among these, UFL1-FHL5 (chr6q16.1) emerged as a genome-wide significant locus in a recent CAD/MI meta-analysis. Here, we use an integrative approach leveraging human genetics, epigenomic profiling, and in vitro functional and ex vivo imaging analyses to prioritize FHL5 as the top candidate causal gene and reveal the molecular mechanisms of its pleiotropic genetic associations. Notably, FHL5 overexpression in coronary artery smooth muscle cells (SMC) increased vascular calcification and dysregulated processes related to extracellular matrix organization and calcium handling. Lastly, by mapping FHL5 binding sites genome-wide using CUT&RUN, we identified regulatory interactions with downstream disease loci having putative roles in SMC phenotypic modulation. Together, these trans-acting mechanisms may account for a portion of the heritable risk for CAD/MI and other complex vascular diseases.
2022-10-31 | GSE201570 | GEO
Project description:Coronary artery disease (CAD) is a complex inflammatory disease of the vessel wall and often leads to myocardial infarction. Genome-wide association studies (GWAS) have now identified over 200 genetic loci associated with CAD. The majority of CAD-associated variants are located in noncoding regions of the genome, many of which are predicted to regulate chromatin accessibility and gene expression. In this study, we performed ATAC-seq in human coronary artery patient samples to identify novel chromatin accessibility QTLs (caQTLs) and gain additional insights into CAD regulatory mechanisms in vivo.
2022-01-24 | GSE188422 | GEO
Project description:Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in coronary artery disease (CAD). However, non-European populations are underrepresented in GWAS and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotype information to identify quantitative trait loci (QTL) for gene expression and splicing in coronary arteries obtained from 138 ancestrally diverse Americans.
2023-11-14 | GSE225650 | GEO
Project description:Identification of causal variants and mechanisms underlying complex disease traits in humans requires strategies to locate and fine-map functional regulatory variants in disease-relevant cell types. To discover functional regulatory variants in primary aortic endothelial cells (ECs) from humans, we collected genetic, transcriptomic, and four epigenomic phenotypes in a population of up to 150 human donors representing individuals of both sexes and three major ancestries. We found thousands of EC eQTLs that were not present in GTEx at all ranges of effect sizes, indicating novel functional variants not observable from tissue data. We performed several epigenetic assays across 53 donors’ EC to enable molecular QTL mapping, which included chromatin accessibility, histone modification, and transcription factor binding of proteins ERG and NF-kB/p65 in two activation states. We discovered over 3000 regulatory elements where cis-regulatory variants associated to significant differences in epigenetic marks. Co-localization with our eQTLs, TF motif mutations, and 3D confirmation capture data in ECs enabled our discovery of hundreds of high-confidence functional regulatory elements that perturb endothelial molecular phenotypes. Furthermore, this set of variants is enriched at GWAS loci for Coronary Artery disease and other disease traits, with some SNPs demonstrating pleiotropic effects. Together, our dataset and analytical approach provide the genetics and vascular biology communities with specific variants affecting EC biology and serves as a proof-of-principle for how to detect functional regulatory variants in human cells with relevance to complex traits.
2020-06-02 | GSE139377 | GEO
Project description:Genome-wide association studies (GWAS) have identified hundreds of coronary artery disease (CAD) associated variants; however, the regulatory mechanisms for candidate variants remain mostly unknown. In this study, we evaluated the epigenomic landscape in coronary artery segments using the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq), addressed how chromatin accessibility in human coronary arteries differs from healthy vs ischemic heart derived-coronary arteries, and defined how chromatin accessibility can be used to understand mechanisms of CAD GWAS results. We report 12,226 control-specific (Con) and 1,023 Ischemic-specific (Isc) differentially accessible regions (DARs) in human coronary arteries. Isc tissue samples were enriched for immune cell activation and ~300 CAD-associated variants were mapped in DARs. We also identified CAD-associated variants predicted to alter transcripion factor binding sites related to CAD. Additionally, we identified endothelial/smooth-muscle-associated genes proximal to Con-DARs and CAD-associated genes proximal to Isc-DARs. In summary, we provide an initial analysis of chromatin accessibility in heathy and atherosclerotic human coronary artery tissue, prioritizing CAD GWAS variants for downstream investigation by altering atherosclerosis-related cis-regulatory activity, and present hypotheses for regulatory mechanisms that could impact CAD progression.
2026-01-16 | GSE273054 | GEO
Project description:Coronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across several cell types. Genome-wide association studies (GWAS) have identified over 170 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis-regulatory elements (CREs). Here, we applied single-cell ATAC-seq to profile 28,316 cells across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters. We mapped ~320,000 accessible sites across all cells, identified cell type-specific elements, transcription factors, and prioritized functional CAD risk variants via quantitative trait locus and sequence-based predictive modeling. We identified a number of candidate mechanisms for smooth muscle cell transition states and identified putative binding sites for risk variants. We further employed CRE to gene linkage to nominate disease-associated key driver transcription factors such as PRDM16 and TBX2. This single cell atlas provides a critical step towards interpreting cis-regulatory mechanisms in the vessel wall across the continuum of CAD risk.
2021-12-14 | GSE175621 | GEO
Project description:Background: Coronary artery disease (CAD) is a genetically complex condition and remains the leading cause of mortality worldwide. Genome-wide association studies (GWAS) have identified a CAD risk locus on chromosome 10q23 that is independent of traditional risk factors, providing an opportunity to uncover novel molecular mechanisms contributing to CAD pathogenesis. Methods: Improved fine-mapping approaches were used to prioritize noncoding variants at the 10q23 locus within the intronic region of Tetraspanin 14 (TSPAN14). Regulatory elements harboring lead variants were functionally interrogated using chromatin accessibility and CRISPR-mediated deletion approaches in endothelial cells (ECs). Subsequently, TSPAN14 function in ECs was assessed using transcriptomic profiling, Notch signaling activation assays, and EC functional assay using gene knockout (KO) cell lines. Results: Fine-mapping identified two lead variants, rs17680741 and rs12260962, located within regulatory elements predicted to affect TSPAN14 expression in monocytes and ECs, respectively. Chromatin accessibility and enhancer deletion assays demonstrated EC-specific function for rs12260962-harboring regulatory element in TSPAN14 expression regulation. Loss of TSPAN14 resulted in significant transcriptomic changes related to Notch signaling, heart morphogenesis, cell adhesion, and wound healing. Functionally, TSPAN14 KO ECs exhibited impaired cell-cell junction integrity, reduced repair capacity, and diminished mechanosensitive responses. Conclusions: Together, these data identify a regulatory element harboring CAD-associated variants at the 10q23 locus that modulates TSPAN14 expression and downstream Notch signaling in ECs, thereby linking genetic risk to endothelial dysfunction relevant to CAD pathogenesis.
2026-05-15 | GSE318807 | GEO