Journal Article

DKFZ-2022-01479

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.

Banday, A. R. ; Stanifer, M. L. ; Florez-Vargas, O. ; Onabajo, O. O. ; Papenberg, B. W. ; Zahoor, M. A. ; Mirabello, L. ; Ring, T. J. ; Lee, C.-H. ; Albert, P. S. ; Andreakos, E. ; Arons, E. ; Barsh, G. ; Biesecker, L. G. ; Boyle, D. L. ; Brahier, M. S. ; Burnett-Hartman, A. ; Carrington, M. ; Chang, E. ; Choe, P. G. ; Chisholm, R. L. ; Colli, L. M. ; Dalgard, C. L. ; Dude, C. M. ; Edberg, J. ; Erdmann, N. ; Feigelson, H. S. ; Fonseca, B. A. ; Firestein, G. S. ; Gehring, A. J. ; Guo, C.DKFZ* ; Ho, M. ; Holland, S. ; Hutchinson, A. A. ; Im, H. ; Irby, L. ; Ison, M. G. ; Joseph, N. T. ; Kim, H. B. ; Kreitman, R. J. ; Korf, B. R. ; Lipkin, S. M. ; Mahgoub, S. M. ; Mohammed, I. ; Paschoalini, G. L. ; Pacheco, J. A. ; Peluso, M. J. ; Rader, D. J. ; Redden, D. T. ; Ritchie, M. D. ; Rosenblum, B. ; Ross, M. E. ; Anna, H. P. S. ; Savage, S. A. ; Sharma, S. ; Siouti, E. ; Smith, A. K. ; Triantafyllia, V. ; Vargas, J. M. ; Vargas, J. D. ; Verma, A. ; Vij, V. ; Wesemann, D. R. ; Yeager, M. ; Yu, X. ; Zhang, Y. ; Boulant, S.DKFZ* ; Chanock, S. J. ; Feld, J. J. ; Prokunina-Olsson, L.

2022
Macmillan Publishers Limited, part of Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41588-022-01113-z

Abstract: The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.

Note: 2022 Aug;54(8):1103-1116

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Contributing Institute(s):

1. NWG Infection and Immune Sensing Dynamics (F140)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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