Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA354109 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MGH AF Study: Exome Sequencing in Early-Onset Atrial Fibrillation
| PRJNA354107 | ENA
Project description:Atrial fibrillation (AF) is the most common abnormality of heart rhythm and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies (GWAS) increased the power to detect single-nucleotide variant (SNV) associations, and we report more than 350 AF-associated genetic loci. At 139 loci we identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication. We next assayed chromatin accessibility by ATAC-seq and histone H3 Lysine 4 trimethylation in stem cell derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility of our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, we found that a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known AF risk loci will facilitate a greater understanding of the pathways underlying this heart rhythm disorder.
2024-02-08 | GSE225293 | GEO
Project description:<p>The Massachusetts General Hospital (MGH) Atrial Fibrillation Study was initiated in 2001. The study has enrolled serial probands, unaffected and affected family members with atrial fibrillation. At enrollment participants undergo a structured interview to systematically capture their past medical history, AF treatments, and family history. An electrocardiogram is performed; the results of an echocardiogram are obtained; and blood samples are obtained.</p> <p><b>The Massachusetts General Hospital (MGH) Atrial Fibrillation Study is utilized in the following dbGaP substudies.</b> To view genotypes, analysis, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs001001 Massachusetts General Hospital (MGH) Atrial Fibrillation Study. <ul> <li><a href="./study.cgi?study_id=phs001116">phs001116</a> MGH AF CHARGE-S</li> <li><a href="./study.cgi?study_id=phs001117">phs001117</a> MGH AF Exome Sequencing</li> <li><a href="./study.cgi?study_id=phs001118">phs001118</a> MGH AF Medical Resequencing</li> </ul> </p>
| phs001001 | dbGaP
Project description:Atrial fibrillation (AF) is the most common heart arrhythmia disease. The greatest risk of atrial fibrillation is stroke, and stroke caused by valvular heart disease with atrial fibrillation (AF-VHD) is more serious. the development mechanism from VHD to AF-VHD is not yet clear. The research on expression profiles of lncRNA and mRNA is helpful to explore molecular mechanism in patients with valvular heart disease who develop atrial fibrillation.
2018-04-12 | GSE113013 | GEO
Project description:Atrial fibrillation (AF) is the most common persistent arrhythmia that affect 1–2% of the general population. People with AF display an array of complications cardiogenic stroke and systemic embolism caused by hemodynamic instability and blood hypercoagulability in clinical practice. However, it’s still unclear whether and how ubiquitylated proteins react to AF in the left atrial appendage of patients with AF and valvular heart disease. This theory focuses on the changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease. We firstly widely analysis the proteins ubiquitination in patients with atrial fibrillation.
2021-12-24 | PXD030397 | Pride
Project description:Atrial fibrillation (AF) is the most common arrhythmia in the world, and is linked to significant morbidity and mortality. Despite advances in the treatment and management of AF, important challenges remain for patients. Human genetics can provide strong therapeutic candidates, but the identification of the causal genes and their functions is difficult. Here, we apply an AF fine-mapping strategy that leverages results from a cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) from left atrial appendages (LAA) obtained from two cohorts with distinct ancestry (European and East Asian), and a paired RNAseq and ATACseq LAA single-nucleus assay (sn-multiome). We found that AF-associated LAA eQTLs are largely consistent across ancestries. At ten AF loci, our co-localization and fine-mapping analyses implicated 14 genes. Furthermore, by integrating our LAA sn-multiome data and other epigenomic datasets with our fine-mapping results, we identified four primary candidate causal AF variants, including rs7612445 at GNB4 and rs242557 at MAPT, for which we propose molecular mechanisms of AF-association at the cellular level. Finally, we showed that the repression of the strongest AF-associated eQTL gene, LINC01629, in human embryonic stem cell-derived cardiomyocytes using CRISPR inhibition results in the dysregulation of pathways linked to genes involved in the development of atrial tissue and the cardiac conduction system (e.g. HCN4, PITX2 and TBX5).
2024-07-09 | GSE238242 | GEO
Project description:Atrial fibrillation (AF) is the most common arrhythmia in the world, and is linked to significant morbidity and mortality. Despite advances in the treatment and management of AF, important challenges remain for patients. Human genetics can provide strong therapeutic candidates, but the identification of the causal genes and their functions is difficult. Here, we apply an AF fine-mapping strategy that leverages results from a cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) from left atrial appendages (LAA) obtained from two cohorts with distinct ancestry (European and East Asian), and a paired RNAseq and ATACseq LAA single-nucleus assay (sn-multiome). We found that AF-associated LAA eQTLs are largely consistent across ancestries. At ten AF loci, our co-localization and fine-mapping analyses implicated 14 genes. Furthermore, by integrating our LAA sn-multiome data and other epigenomic datasets with our fine-mapping results, we identified four primary candidate causal AF variants, including rs7612445 at GNB4 and rs242557 at MAPT, for which we propose molecular mechanisms of AF-association at the cellular level. Finally, we showed that the repression of the strongest AF-associated eQTL gene, LINC01629, in human embryonic stem cell-derived cardiomyocytes using CRISPR inhibition results in the dysregulation of pathways linked to genes involved in the development of atrial tissue and the cardiac conduction system (e.g. HCN4, PITX2 and TBX5).
2024-07-09 | GSE271839 | GEO
Project description:NHLBI TOPMed - Centers for Common Disease Genomics (CCDG): Massachusetts General Hospital Atrial Fibrillation (MGH AF) Study
| PRJNA309735 | ENA
Project description:Atrial fibrillation (AF) is currently the most prevalent arrhythmia worldwide.Recent clinical data implicate the additional contribution of non-coding RNAs in the pathogenesis of AFï¼which include microRNAs(miRNAs), endogenous small interfering RNAs, PIWIinteracting RNAs, and lncRNA. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with AF has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNA and mRNA expression profiles in myocardial sleevesof pulmonary veins between the patients who develop AF and the patients who were in normal sinus rhythm, which was performed using a second generation lncRNA microarrayï¼focusing specifically on the identification and characterization of lncRNAs and mRNA potentially involving in maintaining atrial fibrillation. We conducted an integrated analysis of myocardial sleeves of pulmonary veinsï¼PVsï¼from 12 patients (6 non-AF and 6AF) in our center, of which hypertension, diabetes, smoking and alcohol abuse were excluded, using a second generation lncRNA microarray
2016-01-16 | E-GEOD-76899 | biostudies-arrayexpress
Project description:Genome-wide association studies (GWAS) have linked hundreds of loci to cardiac diseases. However, in most loci the causal variants and their target genes remain unknown. We developed a combined experimental and analytical approach that integrates single cell epigenomics with GWAS to prioritize risk variants and genes. We profiled accessible chromatin in single cells obtained from human hearts and leveraged the data to study genetics of Atrial Fibrillation (AF), the most common cardiac arrhythmia. Enrichment analysis of AF risk variants using cell-type-resolved open chromatin regions (OCRs) implicated cardiomyocytes as the main mediator of AF risk. We then performed statistical fine-mapping, leveraging the information in OCRs, and identified putative causal variants in 122 AF-associated loci. Taking advantage of the fine-mapping results, our novel statistical procedure for gene discovery prioritized 45 high-confidence risk genes, highlighting transcription factors and signal transduction pathways important for heart development. We further leveraged our single-cell data to study genetics of gene expression. An unexpected finding from earlier studies is that expression QTLs (eQTLs) are often shared across tissues even though most regulatory elements are cell-type specific. We found that this sharing is largely driven by the limited power of eQTL studies using bulk tissues to detect cell-type-specific regulatory variants. This finding points to an important limitation of using eQTLs to interpret GWAS of complex traits. In summary, our analysis provides a comprehensive map of AF risk variants and genes, and a general framework to integrate single-cell genomics with genetic studies of complex traits.
2023-02-12 | GSE224996 | GEO