A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity.

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Serval ID
serval:BIB_D4F6D811B9B4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Production externe
Title
A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity.
Journal
Nature medicine
Author(s)
Zhou S., Butler-Laporte G., Nakanishi T., Morrison D.R., Afilalo J., Afilalo M., Laurent L., Pietzner M., Kerrison N., Zhao K., Brunet-Ratnasingham E., Henry D., Kimchi N., Afrasiabi Z., Rezk N., Bouab M., Petitjean L., Guzman C., Xue X., Tselios C., Vulesevic B., Adeleye O., Abdullah T., Almamlouk N., Chen Y., Chassé M., Durand M., Paterson C., Normark J., Frithiof R., Lipcsey M., Hultström M., Greenwood CMT, Zeberg H., Langenberg C., Thysell E., Pollak M., Mooser V., Forgetta V., Kaufmann D.E., Richards J.B.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
04/2021
Peer-reviewed
Oui
Volume
27
Number
4
Pages
659-667
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10 <sup>-8</sup> ), hospitalization (OR = 0.61, P = 8 × 10 <sup>-8</sup> ) and susceptibility (OR = 0.78, P = 8 × 10 <sup>-6</sup> ). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.
Keywords
2',5'-Oligoadenylate Synthetase/genetics, 2',5'-Oligoadenylate Synthetase/physiology, Aged, Aged, 80 and over, Animals, COVID-19/etiology, COVID-19/genetics, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Interleukin-10 Receptor beta Subunit/genetics, Male, Mendelian Randomization Analysis, Middle Aged, Neanderthals, Protein Isoforms/physiology, Quantitative Trait Loci, SARS-CoV-2, Severity of Illness Index, White People
DOI
10.1038/s41591-021-01281-1
Pubmed
33633408
Web of science
000621738800001
Publisher's website
http://europepmc.org/abstract/med/33633408
Create date
09/05/2023 13:59
Last modification date
29/11/2024 14:40
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