Parkinson's disease risk enhancers in microglia.
iScience
; 27(2): 108921, 2024 Feb 16.
Article
em En
| MEDLINE
| ID: mdl-38323005
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Idioma:
En
Revista:
IScience
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos