Genome-wide association study of long COVID

作者：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, Jens Wiltfang, Jochen Schneider, Thomas G. Schulze, Christof Winter, Ewa Wallin, Robert Frithiof, Fanny Senner, Christoph D. Spinner, Ulrike Protzer, Mattia Cordioli, Nikola S. Mueller, Andreas Dinkel, Janos L. Kalman, Tomislav Maricic, Kristina Adorjan, Miklos Lipcsey, Lisa Fricke, Ing-Marie Larsson, Urs Heilbronner, Monika Budde, Johanna Erber, Tirschenreuth Study (TiKoCo), TwinsUK, Nicholas R. Harvey, UK Biobank (UKB), Vince Forgetta, UnderstandingSociety: UK Household Longitudinal Study, Benedict Hignell, COVID-19 Genomics Network (C19-GenoNet), Yolanda Espinosa-Parrilla, Juan M. Saez Hidalgo, Estefania Nova-Lamperti, Scarlett Gutiérrez-Richards, Gerardo Donoso, Leslie C. Cerpa, Cesar A. Echeverria, Camilo Cabrera, Pamela Bocchieri, Macarena Fuentes-Guajardo, Christian A. Muñoz, Karen Y. Oróstica, Alvaro Figueroa, Lissette G. Guajardo, Iskra A. Signore, Virginia A. Monardes-Ramírez, Eduardo A. Tobar-Calfucoy, Luis A. Quiñones, Cristian E. Yáñez, Daniela Zapata-Contreras, Paula Zuñiga-Pacheco, Romina Quiroga, Matías F. Martínez, Teresa A. Alarcon, Andrea X. Silva, Carolina S. Selman, Sergio Sanhueza, Rocío Retamales-Ortega, Tamara V. Arévalo, Eduardo Lamoza, Héctor Valenzuela-Jorquera, COVID-19 Host Immune Response Pathogenesis Study (CHIRP), Maria Sophia Donaire, Sannidhi Sarvadhavabhatla, Sisse R. Ostrowski, Søren Brunak, David Westergaard, Bjarke Feenstra, Anne Sofie B. Mortensen, Extended Cohort for E-health, Environment and DNA (EXCEED), Anna L. Guyatt, Genomes for Life (GCAT) and Cohort COVID in Catalonia (COVICAT study), Rafael de Cid, Susana Iraola-Guzmán, Gemma Moncunill, Alba Blasco, Judith Garcia-Aymerich, Natalia Blay, Carlota Dobaño, Anna Carreras, Xavier Farré, Manolis Kogevinas, Gemma Castaño-Vinyals, Simone Furini, Chiara Fallerini, Kristina Zguro, Margherita Baldassarri, Francesca Colombo, Genetics of Long Covid (GOLD), Thompson Hannah, Genotek, Anna Ilinskaya, Michil Trofimov, Layal Shaheen, Nikolay Plotnikov, Anna Kim, Dmitrii Kharitonov, Valery Ilinsky, Alexei Kamelin, Helix–Helix Exome+ and Healthy Nevada Project COVID-19 Phenotypes, Francisco Tanudjaja, Efren Sandoval, Nicole L. Washington, Simon White, Iva Neveux, Shaun Dabe, Alexandre Bolze, Kelly M. Schiabor Barrett, Covid-19 Ioannina Biobank, Eirini Christaki, Haralampos Milionis, Ioanna Tzoulaki, Angelos Liontos, Evangelos Evangelou, Evangelia Ntzani, Genome-wide assessment of the gene variants associated with severe COVID-19 phenotype in Iran (IrCovid), Rasoul Aliannejad, Vahideh Zarei, Nastaran Soltani, Bahareh Sharififard, Hengameh Ansari Tadi, Ali Amirsavadkouhi, Japan COVID-19 Task Force, Ho NamKoong, Lifelines, Mount Sinai COVID Biobank (MSCIC), Ryan C. Thompson, Alexander W. Charney, Laura G. Sloofman, Nicole W. Simons, PHOSP-COVID Collaborative Group, GENCOV Study, Olga Vishnyakova, Xu Xinyi, Jennifer Taher, Lloyd T. Elliott, Genome Database of the Latvian Population (LGDB), Vita Rovite, Peculis Raitis, Monta Briviba, Janis Klovinš, MassGeneralBrigham (MGB), Richa Saxena, Angus C. Burns, Jakob M. Cherry, Matthew Maher, Arne Kukkonen, Fondazione COVID-19 Genomic Study (FOGS), Mauro Tettamanti, Luisa Ronzoni, Daniele Prati, Flora Peyvandi, Rossana Carpani, Antonio Muscatello, Sara Margarita, Francesco Malvestiti, Giuseppe Lamorte, Marco Mantero, Andre Franke, David Ellinghaus, Nathalie Iannotti, Nicola Montano, Alessandro Nobili, Frauke Degenhardt, Alessandra Bandera, Fabio Blandini, Francesco Bruno Arturo Blasi, Tom Hemming Karlsen, Shiuh‐Wen Luoh, Christian Erikstrup, Ole Birger Pedersen, Jordan Lerner‐Ellis, Alicia Colombo, Joseph J. Grzymski, Makoto Ishii, Yukinori Okada, Noam D. Beckmann, Meena Kumari, Ralf Wagner, Iris M. Heid, Catherine John, Patrick Short, Per Magnus, Laura Ansone, Luca Valenti, Sulggi A. Lee, Louise V. Wain, Ricardo A. Verdugo, Karina Banasik, Frank Geller, Lude Franke, Alexander Rakitko, Emma L. Duncan, Alessandra Renieri, Konstantinos K. Tsilidis, Rafael de Cid, Ahmadreza Niavarani, Erik Abner, Teresa Tusié‐Luna, Shefali S. Verma, George Davey Smith, Nicholas J. Timpson, Ravi Madduri, Kelly Cho, Mark J Daly, Andrea Ganna, Eva C. Schulte, J. Brent Richards, Kerstin U. Ludwig, Michael Hultström, Hugo Zeberg, Hanna M. Ollila · 发表于：Nature Genetics · 年份：2025 · DOI：10.1038/s41588-025-02100-w · 被引用次数：39 · 研究领域：Long-Term Effects of COVID-19、Inflammasome and immune disorders、Autoimmune and Inflammatory Disorders Research

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.