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

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• dc.contributor.author Stikker, Bernard S.
• dc.contributor.author Stik, Grégoire
• dc.contributor.author van Ouwerkerk, Antoinette F.
• dc.contributor.author Trap, Lianne
• dc.contributor.author Spicuglia, Salvatore
• dc.contributor.author Hendriks, Rudi W.
• dc.contributor.author Stadhouders, Ralph
• dc.date.accessioned 2022-05-30T10:28:21Z
• dc.date.available 2022-05-30T10:28:21Z
• dc.date.issued 2022
• dc.description.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.
• dc.description.sponsorship B.S. and R.W.H. are supported by Dutch Lung Foundation grant 4.1.18.226. G.S. was supported by the ‘Fundación Científica de la Asociación Española Contra el Cáncer’. R.S. is supported by an Erasmus MC Fellowship, a Dutch Lung Foundation Junior Investigator grant (4.2.19.041JO) and a VIDI grant (09150172010068) from the Dutch Research Council (NWO). A.F.v.O. was supported by a postdoctoral fellowship from the Foundation Recherche Médicale. S.S. was supported by an Agence National pour la Recherche” grant (ANR-18-CE12-0019)
• dc.format.mimetype application/pdf
• dc.identifier.citation Stikker BS, Stik G, van Ouwerkerk AF, Tap L, Spicuglia S, Hendrinks RW et al.Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages. Genome Biol. 2022 Apr 14;23(1):96. DOI:10.1186/s13059-022-02669-z .
• dc.identifier.doi http://dx.doi.org/10.1186/s13059-022-02669-z
• dc.identifier.issn 1474-7596
• dc.identifier.uri http://hdl.handle.net/10230/53309
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.rights © Bernard S. Stikker et al. 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other COVID-19 (Malaltia)
• dc.subject.other Genètica
• dc.subject.other Genòmica
• dc.title Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion