Genome-wide association study of long COVID

Macarena Fuentes-Guajardo; Fondazione COVID-19 Genomic Study (FOGS)

doi:10.1038/s41588-025-02100-w

Genome-wide association study of long COVID

Título traducido de la contribución: Estudio de asociación de todo el genoma de la COVID prolongada

Macarena Fuentes-Guajardo
, Fondazione COVID-19 Genomic Study (FOGS)

Departamento de Tecnología Médica

University of Helsinki
McGill University
Kyoto University
The University of Tokyo
Japan Society for the Promotion of Science
University of California at San Francisco
University of Milan
Broad Institute
Massachusetts General Hospital
Germans Trias i Pujol Research Institute (IGTP)
Grup de REcerca en Impacte de les Malalties Cròniques i les seves Trajectòries (GRIMTra)
Sano Genetics Limited
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Icahn School of Medicine at Mount Sinai
Harvard University
University of Bonn
University of Bristol
University of Ioannina
King's College London
Universidad Nacional Autónoma de México
Fred Hutchinson Cancer Research Center
University of Washington
Helix OpCo LLC
University of Bergen
Norwegian Institute of Public Health
University of Edinburgh
Mydnavar
Helsinki University Central Hospital
Department of Veterans Affairs
Argonne National Laboratory
University of Leicester
University Hospitals of Leicester NHS Trust
National Research Council of Italy
University of Essex
University of Groningen
Oncode Investigator
University of Copenhagen
University of Regensburg
Latvian Biomedical Research and Study Centre
Brigham and Women’s Hospital
University of California at Berkeley
Universidad de Chile
University of Toronto
University of Pennsylvania
Genotek
Queen Mary University of London
IRCCS Istituto Giannina Gaslini - Genova
International Islamic University Malaysia
All India Institute of Medical Sciences, Patna
Universiti Malaysia Pahang Al-Sultan Abdullah
The University of Osaka
Keio University
Nagoya University
University of Marburg
Université Laval
Centre Hospitalier de L'Universite de Montreal
Louis Stokes Cleveland VA Medical Center
Case Western Reserve University
Portland VA Medical Center
Universidad Austral de Chile
Universidad de Concepción
Arturo López Pérez Foundation
Vicerrectoría de Investigación Desarrollo y Creación Artística
Docente y de Investigación (CADI-UMAG)
Universidad de Magallanes
Hospital del Salvador
Universidad de Atacama
Universidad de Talca
Universidad de Antofagasta
Interuniversity Center on Healthy Aging
University of Montreal
Technical University of Munich
Ludwig Maximilian University of Munich
Uppsala University
University of Bern
Max Planck Institute for Evolutionary Anthropology
Helmholtz Zentrum München - German Research Center for Environmental Health
Helmholtz Centre for Infection Research
Johns Hopkins University
SUNY Upstate Medical University
Heidelberg University
University of Göttingen
German Center for Neurodegenerative Diseases
University of Aveiro
Max Planck Institute of Psychiatry
University of California at Los Angeles
Universidad Autónoma Metropolitana
ISGlobal
Pompeu Fabra University
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Hospital del Mar
Genomes for Life-GCAT lab
(2021 SGR 01537)
CIBER de Enfermedades Infecciosas (CIBERINFEC)
Statens Serum Institut
Noorafshar Hospital
Tehran University of Medical Sciences
Brown University
Imperial College London
Academy of Athens
Renown Health
University of Nevada, Reno
Eligens SIA
University of Siena
Azienda Ospedaliera Universitaria Senese
University of Bologna
Simon Fraser University
Guy's and St Thomas' NHS Foundation Trust
IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano
University of Oslo
IRCCS Istituto di ricerche farmacologiche Mario Negri - Milano, Bergamo, Ranica
University of Tartu
Oregon Health and Science University
Aarhus University
Sjællands Universitetshospital
RIKEN
Karolinska Institutet

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30 Citas (Scopus)

Resumen

Las infecciones pueden provocar síntomas y enfermedades persistentes, como herpes zóster tras varicela zóster o fiebre reumática tras infecciones estreptocócicas. De forma similar, la infección por el coronavirus 2 del síndrome respiratorio agudo severo (SARS‑CoV‑2) puede provocar la enfermedad por coronavirus prolongada (COVID), que se manifiesta típicamente como fatiga, síntomas pulmonares y disfunción cognitiva. Los mecanismos biológicos detrás de la COVID prolongada siguen sin estar claros. Realizamos un estudio de asociación de todo el genoma para la COVID prolongada, que incluyó hasta 6450 casos de COVID prolongada y 1 093 995 controles poblacionales de 24 estudios en 16 países. Descubrimos una asociación de FOXP4 con la COVID prolongada, independientemente de su asociación previamente identificada con la COVID-19 grave. La señal se replicó en 9500 casos de COVID prolongada y 798 835 controles poblacionales. Dado el papel del factor de transcripción FOXP4 en la fisiología y patología pulmonar, nuestros hallazgos destacan la importancia de la función pulmonar en la fisiopatología de la COVID prolongada.

Título traducido de la contribución	Estudio de asociación de todo el genoma de la COVID prolongada
Idioma original	Inglés
Páginas (desde-hasta)	1402-1417
Número de páginas	16
Publicación	Nature Genetics
Volumen	57
N.º	6
DOI	https://doi.org/10.1038/s41588-025-02100-w
Estado	Publicada - jun 2025

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title = "Genome-wide association study of long COVID",

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{\textquoteright}s role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.",

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AU - Jones, Samuel E.

AU - Andrews, Shea J.

AU - Fuentes-Guajardo, Macarena

AU - Fondazione COVID-19 Genomic Study (FOGS)

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AB - 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.

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Genome-wide association study of long COVID

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