학술논문
A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity
Document Type
Article
Author
Zhou, Sirui; Butler-Laporte, Guillaume; Nakanishi, Tomoko; Morrison, David R.; Afilalo, Jonathan; Afilalo, Marc; Laurent, Laetitia; Pietzner, Maik; Kerrison, Nicola; Zhao, Kaiqiong; Brunet-Ratnasingham, Elsa; Henry, Danielle; Kimchi, Nofar; Afrasiabi, Zaman; Rezk, Nardin; Bouab, Meriem; Petitjean, Louis; Guzman, Charlotte; Xue, Xiaoqing; Tselios, Chris; Vulesevic, Branka; Adeleye, Olumide; Abdullah, Tala; Almamlouk, Noor; Chen, Yiheng; Chassé, Michaël; Durand, Madeleine; Paterson, Clare; Normark, Johan; Frithiof, Robert; Lipcsey, Miklós; Hultström, Michael; Greenwood, Celia M. T.; Zeberg, Hugo; Langenberg, Claudia; Thysell, Elin; Pollak, Michael; Mooser, Vincent; Forgetta, Vincenzo; Kaufmann, Daniel E.; Richards, J. Brent
Source
Nature Medicine; April 2021, Vol. 27 Issue: 4 p659-667, 9p
Subject
Language
ISSN
10788956; 1546170X
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.