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

Genome Biology

Salvatore Spicuglia¹  Antoinette F. van Ouwerkerk¹  Grégoire Stik²  Bernard S. Stikker³  Rudi W. Hendriks³  Ralph Stadhouders³  Lianne Trap³ 

[1] Aix-Marseille University, INSERM, TAGC, UMR 1090;Centre for Genomic Regulation (CRG) and Institute of Science and Technology (BIST);Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam;

关键词: SARS-CoV-2;    COVID-19;    3p21.31;    GWAS;    Monocyte;    Macrophage;   

DOI  :  10.1186/s13059-022-02669-z

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown