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Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes [RNA-seq]

ABSTRACT: Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes [RNA-seq]

PROVIDER: PRJNA689841 | ENA |

REPOSITORIES: ENA

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Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes

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Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes [ATAC-seq]

Project description:Genome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that AD risk alleles are enriched in myeloid-specific epigenomic annotations. Here, we show that they are specifically enriched in active enhancers of monocytes, macrophages and microglia. We integrated AD GWAS with myeloid epigenomic and transcriptomic datasets using analytical approaches to link myeloid enhancer activity to target gene expression regulation and AD risk modification. We identify AD risk enhancers and nominate candidate causal genes among their likely targets (including AP4E1, AP4M1, APBB3, BIN1, MS4A4A, MS4A6A, PILRA, RABEP1, SPI1, TP53INP1, and ZYX) in twenty loci. Fine-mapping of these enhancers nominates candidate functional variants that likely modify AD risk by regulating gene expression in myeloid cells. In the MS4A locus we identified a single candidate functional variant and validated it in human induced pluripotent stem cell (hiPSC)-derived microglia and brain. Taken together, this study integrates AD GWAS with multiple myeloid genomic datasets to investigate the mechanisms of AD risk alleles and nominates candidate functional variants, regulatory elements and genes that likely modulate disease susceptibility.

2021-01-06 | GSE164314 | GEO

Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes [RNA-seq]

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Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes

Project description:This SuperSeries is composed of the SubSeries listed below.

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Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes.

Project description: Not available

| S-EPMC7955030 | biostudies-literature

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Project description:Ion channel splice array data from temporal cortex brain tissue samples collected from Alzheimer's disease patients. Temporal cortex (Alzheimer's disease affected brain tissue structure) and cerebellum (Alzheimer's disease unaffected brain tissue structure) samples from control subjects were compared to temporal cortex and cerebellum of patients with Alzheimer's disease.

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