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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ATAC-seq)

ABSTRACT: Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ATAC-seq)

PROVIDER: PRJNA733669 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14685302_1.fastq.gz	Fastqsanger.gz
	SRR14685302_2.fastq.gz	Fastqsanger.gz
	SRR14685303_1.fastq.gz	Fastqsanger.gz
	SRR14685303_2.fastq.gz	Fastqsanger.gz
	SRR14685304_1.fastq.gz	Fastqsanger.gz

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus

Project description:Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ChIP-seq)

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus

Project description:To identify a causative variant and effector gene responsible for a 2-fold increased risk of severe COVID-19, a multi-omics platform was deployed. A combination of ATAC-seq, ChIP-seq, Micro Capture-C and NuTi Capture-C were used to characterize a range of cell types, including epithelial, fibroblast, endothelial, immune and erythroid cells.

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (MCC)

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ATAC-seq)

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ChIP-seq)

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus.

Project description:The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial-mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1. We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31-associated risk. Since the 3p21.31 effect is conferred by a gain-of-function, LZTFL1 may represent a therapeutic target.

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