| Literature DB >> 33633408 |
Sirui Zhou1,2, Guillaume Butler-Laporte1,2, Tomoko Nakanishi1,3,4,5, David R Morrison1, Jonathan Afilalo1,2,6, Marc Afilalo1,7, Laetitia Laurent1, Maik Pietzner8, Nicola Kerrison8, Kaiqiong Zhao1,2, Elsa Brunet-Ratnasingham9,10, Danielle Henry1, Nofar Kimchi1, Zaman Afrasiabi1, Nardin Rezk1, Meriem Bouab1, Louis Petitjean1, Charlotte Guzman1, Xiaoqing Xue1, Chris Tselios1, Branka Vulesevic1, Olumide Adeleye1, Tala Abdullah1, Noor Almamlouk1, Yiheng Chen1,3, Michaël Chassé9, Madeleine Durand9, Clare Paterson11, Johan Normark12, Robert Frithiof13, Miklós Lipcsey13,14, Michael Hultström13,15, Celia M T Greenwood1,2,16, Hugo Zeberg17, Claudia Langenberg8,18, Elin Thysell19, Michael Pollak1,20, Vincent Mooser3, Vincenzo Forgetta1, Daniel E Kaufmann9,21, J Brent Richards22,23,24,25.
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 × 10-8), hospitalization (OR = 0.61, P = 8 × 10-8) and susceptibility (OR = 0.78, P = 8 × 10-6). 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.Entities:
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Year: 2021 PMID： 33633408 DOI： 10.1038/s41591-021-01281-1
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440