https://www.nature.com/articles/s41591-021-01281-1.epdfArticleshttps://doi.org/10.1038/s41591-021-01281-11Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada. 2Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada. 3Department of Human Genetics, McGill University, Montréal, Quebec, Canada. 4Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 5Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan. 6Department of Medicine, Division of Cardiology, McGill University, Montréal, Quebec, Canada. 7Department of Emergency Medicine, Jewish General Hospital, McGill University, Montréal, Quebec, Canada. 8MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK. 9Research Centre of the Centre Hospitalier de l’Université de Montréal, Montréal, Quebec, Canada. 10Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, Quebec, Canada. 11SomaLogic, Inc., Boulder, CO, USA. 12Molecular Infection Medicine Sweden (MIMS) and Wallenberg Center for Molecular Medicine, Department of Clinical Microbiology, Section of Infection and Immunology, Umeå University, Umeå, Sweden. 13Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. 14Hedenstierna Laboratory, CIRRUS, Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. 15Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. 16Gerald Bronfman Department of Oncology, McGill University, Montréal, Quebec, Canada. 17Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. 18Computational Medicine, Berlin Institute of Health, Charité University Medicine Berlin, Berlin, Germany. 19Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. 20Departments of Medicine and Oncology, McGill University, Montréal, Quebec, Canada. 21Department of Medicine, Université de Montréal, Montréal, Quebec, Canada. 22Department of Twin Research, King’s College London, London, UK. 23These authors contributed equally: Sirui Zhou, Guillaume Butler-Laporte, Tomoko Nakanishi. ✉e-mail:
brent.richards@mcgill.caTo date, the COVID-19 pandemic has caused more than 2 mil-lion deaths worldwide and infected approximately 100 mil-lion individuals1. Despite the scale of the epidemic, there are, at present, few disease-specific therapies2 to reduce the morbidity and mortality of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Apart from dexamethasone therapy in oxygen-dependent patients3, most clinical trials have shown, at most, mild or inconsistent benefits on disease outcomes4–6. Therefore, validated targets are needed for COVID-19 therapeutic development.One source of such targets is circulating proteins. Recent advances in large-scale proteomics have enabled the measurement of thousands of circulating proteins—and when combined with evidence from human genetics, such targets greatly improve the probability of drug development success7–9. Although de novo drug development will take time, the repurposing of currently available molecules targeting those proteins could provide an accelerated opportunity to deliver new therapies to patients.Nevertheless, because confounding and reverse causation often bias traditional circulating protein studies, methods are needed to A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severitySirui Zhou1,2,23, Guillaume Butler-Laporte 1,2,23, Tomoko Nakanishi 1,3,4,5,23, David R. Morrison 1, Jonathan Afilalo1,2,6, Marc Afilalo1,7, Laetitia Laurent1, Maik Pietzner8, Nicola Kerrison8, Kaiqiong Zhao1,2, Elsa Brunet-Ratnasingham 9,10, Danielle Henry1, Nofar Kimchi1, Zaman Afrasiabi 1, Nardin Rezk 1, Meriem Bouab1, Louis Petitjean 1, Charlotte Guzman 1, Xiaoqing Xue1, Chris Tselios1, Branka Vulesevic1, Olumide Adeleye1, Tala Abdullah1, Noor Almamlouk1, Yiheng Chen1,3, Michaël Chassé9, Madeleine Durand9, Clare Paterson11, Johan Normark12, Robert Frithiof 13, Miklós Lipcsey13,14, Michael Hultström 13,15, Celia M. T. Greenwood 1,2,16, Hugo Zeberg17, Claudia Langenberg 8,18, Elin Thysell19, Michael Pollak1,20, Vincent Mooser3, Vincenzo Forgetta1, Daniel E. Kaufmann 9,21 and J. Brent Richards 1,2,3,22 ✉
