TY  - JOUR
AU  - Banday, A Rouf
AU  - Stanifer, Megan L
AU  - Florez-Vargas, Oscar
AU  - Onabajo, Olusegun O
AU  - Papenberg, Brenen W
AU  - Zahoor, Muhammad A
AU  - Mirabello, Lisa
AU  - Ring, Timothy J
AU  - Lee, Chia-Han
AU  - Albert, Paul S
AU  - Andreakos, Evangelos
AU  - Arons, Evgeny
AU  - Barsh, Greg
AU  - Biesecker, Leslie G
AU  - Boyle, David L
AU  - Brahier, Mark S
AU  - Burnett-Hartman, Andrea
AU  - Carrington, Mary
AU  - Chang, Euijin
AU  - Choe, Pyoeng Gyun
AU  - Chisholm, Rex L
AU  - Colli, Leandro M
AU  - Dalgard, Clifton L
AU  - Dude, Carolynn M
AU  - Edberg, Jeff
AU  - Erdmann, Nathan
AU  - Feigelson, Heather S
AU  - Fonseca, Benedito A
AU  - Firestein, Gary S
AU  - Gehring, Adam J
AU  - Guo, Cuncai
AU  - Ho, Michelle
AU  - Holland, Steven
AU  - Hutchinson, Amy A
AU  - Im, Hogune
AU  - Irby, Les'Shon
AU  - Ison, Michael G
AU  - Joseph, Naima T
AU  - Kim, Hong Bin
AU  - Kreitman, Robert J
AU  - Korf, Bruce R
AU  - Lipkin, Steven M
AU  - Mahgoub, Siham M
AU  - Mohammed, Iman
AU  - Paschoalini, Guilherme L
AU  - Pacheco, Jennifer A
AU  - Peluso, Michael J
AU  - Rader, Daniel J
AU  - Redden, David T
AU  - Ritchie, Marylyn D
AU  - Rosenblum, Brooke
AU  - Ross, M Elizabeth
AU  - Anna, Hanaisa P Sant
AU  - Savage, Sharon A
AU  - Sharma, Sudha
AU  - Siouti, Eleni
AU  - Smith, Alicia K
AU  - Triantafyllia, Vasiliki
AU  - Vargas, Joselin M
AU  - Vargas, Jose D
AU  - Verma, Anurag
AU  - Vij, Vibha
AU  - Wesemann, Duane R
AU  - Yeager, Meredith
AU  - Yu, Xu
AU  - Zhang, Yu
AU  - Boulant, Steeve
AU  - Chanock, Stephen J
AU  - Feld, Jordan J
AU  - Prokunina-Olsson, Ludmila
TI  - Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.
JO  - Nature genetics
VL  - 54
IS  - 8
SN  - 1061-4036
CY  - London
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DKFZ-2022-01479
SP  - 1103-1116
PY  - 2022
N1  - 2022 Aug;54(8):1103-1116
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35835913
DO  - DOI:10.1038/s41588-022-01113-z
UR  - https://inrepo02.dkfz.de/record/180679
ER  -