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

Authors
  • Stikker, Bernard S.
  • Stik, Grégoire
  • van Ouwerkerk, Antoinette F.
  • Trap, Lianne
  • Spicuglia, Salvatore
  • Hendriks, Rudi W.
  • Stadhouders, Ralph
Type
Published Article
Publication Date
Apr 14, 2022
Volume
23
Identifiers
DOI: 10.1186/s13059-022-02669-z
PMID: 35421995
PMCID: PMC9009160
Source
PubMed Central
Keywords
Disciplines
  • Short Report
License
Unknown

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. Supplementary Information The online version contains supplementary material available at 10.1186/s13059-022-02669-z.

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