Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages
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authors
keywords
- SARS-CoV-2
- COVID-19
- 3p2131
- GWAS
- Monocyte
- Macrophage
- Chemokine receptor
- 3D genome organization
- CTCF
- Gene regulation
document type
ARTabstract
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.
