%0 Journal Article
%A Banday, A Rouf
%A Stanifer, Megan L
%A Florez-Vargas, Oscar
%A Onabajo, Olusegun O
%A Papenberg, Brenen W
%A Zahoor, Muhammad A
%A Mirabello, Lisa
%A Ring, Timothy J
%A Lee, Chia-Han
%A Albert, Paul S
%A Andreakos, Evangelos
%A Arons, Evgeny
%A Barsh, Greg
%A Biesecker, Leslie G
%A Boyle, David L
%A Brahier, Mark S
%A Burnett-Hartman, Andrea
%A Carrington, Mary
%A Chang, Euijin
%A Choe, Pyoeng Gyun
%A Chisholm, Rex L
%A Colli, Leandro M
%A Dalgard, Clifton L
%A Dude, Carolynn M
%A Edberg, Jeff
%A Erdmann, Nathan
%A Feigelson, Heather S
%A Fonseca, Benedito A
%A Firestein, Gary S
%A Gehring, Adam J
%A Guo, Cuncai
%A Ho, Michelle
%A Holland, Steven
%A Hutchinson, Amy A
%A Im, Hogune
%A Irby, Les'Shon
%A Ison, Michael G
%A Joseph, Naima T
%A Kim, Hong Bin
%A Kreitman, Robert J
%A Korf, Bruce R
%A Lipkin, Steven M
%A Mahgoub, Siham M
%A Mohammed, Iman
%A Paschoalini, Guilherme L
%A Pacheco, Jennifer A
%A Peluso, Michael J
%A Rader, Daniel J
%A Redden, David T
%A Ritchie, Marylyn D
%A Rosenblum, Brooke
%A Ross, M Elizabeth
%A Anna, Hanaisa P Sant
%A Savage, Sharon A
%A Sharma, Sudha
%A Siouti, Eleni
%A Smith, Alicia K
%A Triantafyllia, Vasiliki
%A Vargas, Joselin M
%A Vargas, Jose D
%A Verma, Anurag
%A Vij, Vibha
%A Wesemann, Duane R
%A Yeager, Meredith
%A Yu, Xu
%A Zhang, Yu
%A Boulant, Steeve
%A Chanock, Stephen J
%A Feld, Jordan J
%A Prokunina-Olsson, Ludmila
%T Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.
%J Nature genetics
%V 54
%N 8
%@ 1061-4036
%C London
%I Macmillan Publishers Limited, part of Springer Nature
%M DKFZ-2022-01479
%P 1103-1116
%D 2022
%Z 2022 Aug;54(8):1103-1116
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35835913
%R 10.1038/s41588-022-01113-z
%U https://inrepo02.dkfz.de/record/180679