Genome-wide association study of long COVID
Vilma Lammi, Tomoko Nakanishi, Samuel E. Jones, Shea J. Andrews, Juha Karjalainen, Beatriz Cortés, Heath O’Brien, Ana Ochoa-Guzmán, Brian Fulton‐Howard, Martin Broberg, Hele Haapaniemi, Masahiro Kanai, Matti Pirinen, Axel Schmidt, Ruth E. Mitchell, Abdou Mousas, Massimo Mangino, Alicia Huerta‐Chagoya, Nasa Sinnott-Armstrong, Elizabeth T. Cirulli, Marc Vaudel, Alex S. F. Kwong, Amit K. Maiti, M. Marttila, Daniel Posner, Alexis Rodriguez, Chiara Batini, Francesca Minnai, Anna Dearman, Robert Warmerdam, Celia Burgos Sequeros, Thomas W. Winkler, Daniel M. Jordan, Raimonds Reščenko, Lorenzo Miano, Jacqueline M. Lane, Ryan Chung, Beatriz Guillén‐Guío, Olivia C. Leavy, Laura Carvajal-Silva, Kevin Aguilar-Valdés, Erika Frangione, Lindsay Guare, Ekaterina Vergasova, Eirini Marouli, Pasquale Striano, Ummu Afeera Zainulabid, Ashutosh Kumar, Hajar Fauzan Ahmad, Ryuya Edahiro, Shuhei Azekawa, Long COVID Host Genetics Initiative, FinnGen, Mari E. K. Niemi, Avon Longitudinal Study of Parents and Children (ALSPAC), Banque québécoise de la COVID-19 (BQC19), Janick St-Cyr, Darin Adra, Madeleine Durand, David Bujold, Guillaume Bourque, Ariane Boisclair, Mylene Bertrand, Daniel Auld, Laetitia Laurent, Solomia Yanishevsky, G. Mark Lathrop, Fangyi Shi, Simon Rousseau, Jiannis Ragoussis, Danielle Perley, Vincent Mooser, David R. Morrison, Bonn Study of COVID Genetics (BoSCO), Daniella Balla, Julia Heggemann, Sonja Schultz, Pari Behzad, Markus M. Nöthen, Abigail Miller, Max C. Pensel, Carlo Maj, VA Million Veteran Program, Kelly Cho, Tianxi Cai, Sudha K. Iyengar, MexGen-COVID Initiative, Carlos A. Aguilar Salinas, Seung Hyuk T. Lee, Hortensia Moreno-Macias, Päivi Pajukanta, Michelle Duran-Gomez, Norwegian Mother Father and Child Cohort Study (MoBa), Lill Trogstad, Penn Medicine BioBank (PMBB), Daniel J. Rader, Marylyn D. Ritchie, Anurag Verma, Colleen M. Kripke, Sergi Papiol
Abstract
Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.