Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages.
Bernard S StikkerGrégoire StikAntoinette F van OuwerkerkLianne TrapSalvatore SpicugliaRudi W HendriksRalph StadhoudersPublished in: Genome biology (2022)
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.
Keyphrases
- genome wide
- coronavirus disease
- dendritic cells
- sars cov
- copy number
- genome wide association
- transcription factor
- respiratory syndrome coronavirus
- regulatory t cells
- early onset
- dna methylation
- peripheral blood
- poor prognosis
- clinical trial
- genome wide identification
- oxidative stress
- dna damage
- immune response
- weight gain
- physical activity