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A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity.
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.
  • Zhou S; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Butler-Laporte G; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
  • Nakanishi T; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Morrison DR; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
  • Afilalo J; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Afilalo M; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
  • Laurent L; Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Pietzner M; Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan.
  • Kerrison N; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Zhao K; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Brunet-Ratnasingham E; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
  • Henry D; Department of Medicine, Division of Cardiology, McGill University, Montréal, Quebec, Canada.
  • Kimchi N; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Afrasiabi Z; Department of Emergency Medicine, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Rezk N; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Bouab M; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Petitjean L; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Guzman C; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Xue X; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
  • Tselios C; Research Centre of the Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
  • Vulesevic B; Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, Quebec, Canada.
  • Adeleye O; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Abdullah T; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Almamlouk N; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Chen Y; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Chassé M; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Durand M; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Paterson C; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Normark J; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Frithiof R; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Lipcsey M; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Hultström M; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Greenwood CMT; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Zeberg H; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Langenberg C; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Thysell E; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
  • Pollak M; Research Centre of the Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
  • Mooser V; Research Centre of the Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
  • Forgetta V; SomaLogic, Inc., Boulder, CO, USA.
  • Kaufmann DE; Molecular Infection Medicine Sweden (MIMS) and Wallenberg Center for Molecular Medicine, Department of Clinical Microbiology, Section of Infection and Immunology, Umeå University, Umeå, Sweden.
  • Richards JB; Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Nat Med ; 27(4): 659-667, 2021 04.
Article in English | MEDLINE | ID: covidwho-1104522
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: 2',5'-Oligoadenylate Synthetase / Genetic Predisposition to Disease / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study Topics: Variants Limits: Aged / Animals / Female / Humans / Male / Middle aged Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2021 Document Type: Article Affiliation country: S41591-021-01281-1

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Full text: Available Collection: International databases Database: MEDLINE Main subject: 2',5'-Oligoadenylate Synthetase / Genetic Predisposition to Disease / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study Topics: Variants Limits: Aged / Animals / Female / Humans / Male / Middle aged Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2021 Document Type: Article Affiliation country: S41591-021-01281-1