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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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https://hal-amu.archives-ouvertes.fr/hal-03685514
Contributor : Lionel Spinelli Connect in order to contact the contributor
Submitted on : Thursday, June 2, 2022 - 10:51:26 AM
Last modification on : Wednesday, September 28, 2022 - 3:14:06 PM
Long-term archiving on: : Saturday, September 3, 2022 - 6:48:57 PM

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Distributed under a Creative Commons Attribution 4.0 International License

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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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