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Journal Articles Genome Biology Year : 2022

Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages

Abstract

Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory chromatin hub that controls the activity of several chemokine receptor genes. Risk SNPs colocalize with regulatory elements and are linked to increased expression of CCR1 , CCR2 and CCR5 in monocytes and macrophages. As excessive organ infiltration of inflammatory monocytes and macrophages is a hallmark of severe COVID-19, our findings provide a rationale for the genetic association of 3p21.31 variants with elevated risk of hospitalization upon SARS-CoV-2 infection.
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Dates and versions

hal-03685514 , version 1 (02-06-2022)

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Attribution - CC BY 4.0

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Bernard Stikker, Grégoire Stik, Antoinette van Ouwerkerk, Lianne Trap, Salvatore Spicuglia, et al.. Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages. Genome Biology, 2022, 23 (1), pp.96. ⟨10.1186/s13059-022-02669-z⟩. ⟨hal-03685514⟩
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