Parkinson's Disease Risk Enhancers in Microglia [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1028661 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Parkinson's Disease Risk Enhancers in Microglia
| PRJNA1028658 | ENA
Project description:Parkinson's Disease Risk Enhancers in Microglia [ATAC-seq]
| PRJNA1028660 | ENA
Project description:Genome-wide association studies (GWAS) have uncovered thousands of single nucleotide polymorphisms (SNPs) that are associated with Parkinson's disease (PD) risk. The functions of most of these SNPs, including the cell type they influence, and how they affect PD etiology remain largely unknown. To identify functional SNPs, we aligned PD risk SNPs within active regulatory regions of DNA in microglia, a cell type implicated in PD development. Out of 6,749 ‘SNPs of interest’ from the most recent PD GWAS metanalysis, 73 were located in open regulatory chromatin as determined by both ATAC-seq and H3K27ac ChIP-seq. We identified an active enhancer in microglia in intron two of SNCA that overlaps two PD risk SNPs, rs2737004 and rs2619356. In iPSC-derived microglia, CRISPR/Cas9 deletion of the open chromatin encompassing these SNPs caused reduced expression of multiple genes including SNCA and the adjacent gene MMRN1. Loss of the enhancer also led to upregulation of genes involved in glucose metabolism, a process that is known to be altered in PD patients. Our work expands the role of SNCA in Parkinson’s Disease and provides a connection between PD-associated genetic variants and underlying biology that points to a risk mechanism in microglia.
2024-01-21 | GSE245523 | GEO
Project description:Genome-wide association studies (GWAS) have uncovered thousands of single nucleotide polymorphisms (SNPs) that are associated with Parkinson's disease (PD) risk. The functions of most of these SNPs, including the cell type they influence, and how they affect PD etiology remain largely unknown. To identify functional SNPs, we aligned PD risk SNPs within active regulatory regions of DNA in microglia, a cell type implicated in PD development. Out of 6,749 ‘SNPs of interest’ from the most recent PD GWAS metanalysis, 73 were located in open regulatory chromatin as determined by both ATAC-seq and H3K27ac ChIP-seq. We identified an active enhancer in microglia in intron two of SNCA that overlaps two PD risk SNPs, rs2737004 and rs2619356. In iPSC-derived microglia, CRISPR/Cas9 deletion of the open chromatin encompassing these SNPs caused reduced expression of multiple genes including SNCA and the adjacent gene MMRN1. Loss of the enhancer also led to upregulation of genes involved in glucose metabolism, a process that is known to be altered in PD patients. Our work expands the role of SNCA in Parkinson’s Disease and provides a connection between PD-associated genetic variants and underlying biology that points to a risk mechanism in microglia.
2024-01-21 | GSE245522 | GEO
Project description:Genome-wide association studies have identified thousands of single nucleotide polymorphisms that associate with increased risk for Parkinson's disease (PD), but the functions of most of them are unknown. Using assay for transposase-accessible chromatin (ATAC) and H3K27ac chromatin immunoprecipitation (ChIP) sequencing data, we identified 73 regulatory elements in microglia that overlap PD risk SNPs. To determine the target genes of a "risk enhancer" within intron two of SNCA, we used CRISPR-Cas9 to delete the open chromatin region where two PD risk SNPs reside. The loss of the enhancer led to reduced expression of multiple genes including SNCA and the adjacent gene MMRN1. It also led to expression changes of genes involved in glucose metabolism, a process that is known to be altered in PD patients. Our work expands the role of SNCA in PD and provides a connection between PD-associated genetic variants and underlying biology that points to a risk mechanism in microglia.
| S-EPMC10845915 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-21 | GSE245524 | GEO
Project description:Parkinson's disease is the second most prevalent neurodegenerative disorder, characterized by the degeneration of dopaminergic neurons. Significant improvements in gait balance, particularly step length and velocity, were revealed by less-invasive wireless cortical stimulation. Transcriptome sequencing was performed to demonstrate the cellular mechanism, specifically targeting the primary motor cortex where the stimulation was applied. Our findings indicated that the differentially expressed genes (DEGs), initially down-regulated following Parkinson's disease induction, were subsequently restored to normal levels after cortical stimulation. We propose these DEGs as a potential target for motor disorder treatment in Parkinson's disease. These genes are implicated in crucial processes such as astrocyte-mediated blood vessel development and microglia-mediated phagocytosis of damaged motor neurons, suggesting their significant roles in improvement of behavior disorder. Moreover, these biomarkers not only facilitate rapid and accurate diagnosis of Parkinson's disease but also assist precision medicine approaches.
2024-07-11 | GSE271930 | GEO
Project description:Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms. This SuperSeries is composed of the following subset Series: GSE20168: Transcriptional analysis of prefrontal area 9 in Parkinson's disease GSE20291: Transcriptional analysis of putamen in Parkinson's disease GSE20292: Transcriptional analysis of whole substantia nigra in Parkinson's disease Refer to individual Series
2010-03-23 | E-GEOD-20295 | biostudies-arrayexpress
Project description:Genome wide DNA methylation association analysis of Parkinson's disease and control samples. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in blood samples. Samples included 1001 Parkinson's disease cases and 973 controls.
2020-02-17 | GSE145361 | GEO
Project description:CIDR_Genomic Analysis of Parkinson's Disease
| PRJNA298844 | ENA