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Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C [Hi-C]

ABSTRACT: We used ATAC-seq, RNA-seq, and promoter to create atlases of the regulatory elements to provide context to type 2 diabetes associated variants from publically available genome-wide association studies

ORGANISM(S): Homo sapiens

PROVIDER: GSE262481 | GEO | 2024/07/26

REPOSITORIES: GEO

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Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C [Capture-C]

Project description:We used ATAC-seq, RNA-seq, and promoter to create atlases of the regulatory elements to provide context to type 2 diabetes associated variants from publically available genome-wide association studies

2024-07-26 | GSE262496 | GEO

Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C [RNA-Seq]

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Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C [ATAC-Seq]

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Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C

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Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types.

Project description:BackgroundSARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. COVID-19 disease severity has been associated with some pre-existing conditions and the magnitude of the adaptive immune response to SARS-CoV-2, and a recent genome-wide association study (GWAS) of the risk of critical illness revealed a significant genetic component. To gain insight into how human genetic variation attenuates or exacerbates disease following SARS-CoV-2 infection, we implicated putatively functional COVID risk variants in the cis-regulatory landscapes of human immune cell types with established roles in disease severity and used high-resolution chromatin conformation capture to map these disease-associated elements to their effector genes.ResultsThis functional genomic approach implicates 16 genes involved in viral replication, the interferon response, and inflammation. Several of these genes (PAXBP1, IFNAR2, OAS1, OAS3, TNFAIP8L1, GART) were differentially expressed in immune cells from patients with severe versus moderate COVID-19 disease, and we demonstrate a previously unappreciated role for GART in T cell-dependent antibody-producing B cell differentiation in a human tonsillar organoid model.ConclusionsThis study offers immunogenetic insight into the basis of COVID-19 disease severity and implicates new targets for therapeutics that limit SARS-CoV-2 infection and its resultant life-threatening inflammation.

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Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types [Capture-C]

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