A second update on mapping the human genetic architecture of COVID-19

The COVID-19 Host Genetics Initiative, Leadership, Masahiro Kanai, Shea J. Andrews, Mattia Cordioli, Christine R. Stevens, Benjamin M. Neale, Mark J. Daly, Andrea Ganna, Writing group

98 more authors

Writing group lead, Gita A. Pathak, Writing group member, Akiko Iwasaki, Analysis group, Manuscript analysis team lead, Juha M Karjalainen, Juha Mehtonen, Manuscript analysis team members: Mendelian randomization, Manuscript analysis team members: principal component projection, gene prioritization, Manuscript analysis team members: methods development, Matti Pirinen, Project management group, Project management lead, Project management support, Karolina Chwiałkowska, Amy Trankiem, Mary K. Balaconis, Scientific communication group, Scientific communication lead, Kumar Veerapen, Brooke N. Wolford, Scientific communication member, Hajar Fauzan Ahmad, Kathrin Aprile von Hohenstaufen, Cindy Germaine Boer, Palwendé Romuald Boua, Guillaume Butler‐Laporte, Carmen Lydia Cadilla, Francesca Colombo, Venceslas Douillard, Nicole Dueker, Atanu Kumar Dutta, Yasser Mohamed El-Sherbiny, Madonna M. Eltoukhy, Sahar Esmaeeli, Annika B. Faucon, Marie-Julie Favé, Israel Fernández‐Cadenas, Margherita Francescatto, Laurent C. Francioli, Lude Franke, Macarena Fuentes‐Guajardo, Rocío Gallego Durán, David Gómez-Cabrero, Emi N. Harry, Philip R. Jansen, József L. Szentpéteri, Elżbieta Kaja, Masahiro Kanai, Chloe Kirk, Athanasios Kousathanas, José Eduardo Krieger, Sanjay Kumar Patel, Audrey Lemaçon, Sophie Limou, Píetro Lió, Eirini Marouli, Minttu M. Marttila, Carolina Medina‐Gómez, Yael Michaeli, Isabelle Migeotte, Soumyajit Mondal, Andrés Moreno‐Estrada, Leire Moya, Tomoko Nakanishi, Jamal Nasir, Dorota Pasko, Nathaniel Michael Pearson, Alexandre C. Pereira, James Rush Priest, Vid Prijatelj, Ivana Prokić, Alexander Teumer, Réka Várnai, Manuel Romero-Gómez, Christina Roos, Jeffrey Rosenfeld, Ruolin Li, Eva Christina Schulte, Claudia Schurmann, Bahareh Sedaghati-khayat, Doaa Shaheen, Ilangumaran Shivanathan, Csilla Sipeky, Sirui Zhou, Pasquale Striano, Yosuke Tanigawa, Ulf Landmesser, Luca V. C. Valenti, Lowell Ling, Henry Houlden, John Hardy, Timothy Rutland Walsh, Maurizio Cecconi, Aliya Sailybayeva, Jaime Masjuán, Fouzia Sadiq

2023

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DOI 10.1038/s41586-023-06355-3
Data confidence 85 high
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Abstract

Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development 1 , 2 . Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release 2 . The increased number of candidate genes at the identified loci helped to map three major biological pathways that are involved in susceptibility and severity: viral entry, airway defence in mucus and type I interferon.