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

ABSTRACT: To investigate the potential role of COVID-19 severity associated GWAS signals affecting the cis-regulatory architecure of human immune cell types. We used high-resolution chromatin conformation capture and accessibility to identify potential effector genes

ORGANISM(S): Homo sapiens

PROVIDER: GSE174648 | GEO | 2022/05/10

REPOSITORIES: GEO

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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]

Project description:To investigate the potential role of COVID-19 severity associated GWAS hits affecting the cis-regulatory architecure of human immune cell types. We used high-resolution chromatin conformation capture and accessibility to identify potential effector genes

2022-05-10 | GSE174651 | GEO

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

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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:This SuperSeries is composed of the SubSeries listed below.

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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.

| S-EPMC9164584 | biostudies-literature

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

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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]

Project description: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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High resolution chromosome conformation capture from gene promoters at COVID-19, T1D, AS and RBC GWAS loci

Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. The majority of causative variants lie in regulatory elements that are located some distance from their target genes. High resolution chromosome conformation capture (3C) has proven useful for identifying enhancer-promoter interaction. We employed targeted Capture-C at loci with GWAS for severe COVID-19, Type-1 Diabetes (T1D), Ankylosing spondylitis (AS) and red blood cell traits (RBC)

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

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

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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

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