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Functional characterization of Alzheimer´s disease genetic variants in microglia

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173316 | GEO | 2023/07/28

REPOSITORIES: GEO

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Functional characterization of Alzheimer´s disease genetic variants in microglia

Project description:Alzheimer’s disease (AD) is an age-related neurodegenerative progressive disorder affecting 10% of people over 65. Less than 5% of patients have known causal genetic mutations while the exact cause of AD for the majority of patients, especially the late onset form, is unknown. Large scale epigenomic studies revealed that disease associated SNPs are highly enriched in cell-type-specific cis-regulatory elements. In AD, SNPs are more significantly enriched in the regulatory regions of myeloid lineages rather than the neuronal cells. However, how AD SNPs affect microglia enhancers, and more interestingly differentially affect state-specific enhancers such as activated upon stimulation, e.g. viral infection, remain largely unexplored. In this study we identified cis-regulatory elements in both resting and IFN-beta stimulated microglia and further functionally characterized how regulatory SNPs lead to immune response dysregulation in the pathogenesis of AD.

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