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

Translated title of the contribution: Genome-wide association study of long COVID

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

Department of Medical Technology

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

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Translated title of the contribution	Genome-wide association study of long COVID
Original language	English
Pages (from-to)	1402-1417
Number of pages	16
Journal	Nature Genetics
Volume	57
Issue number	6
DOIs	https://doi.org/10.1038/s41588-025-02100-w
State	Published - Jun 2025

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10.1038/s41588-025-02100-w

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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.",

author = "Vilma Lammi and Tomoko Nakanishi and Jones, \{Samuel E.\} and Andrews, \{Shea J.\} and Macarena Fuentes-Guajardo and \{Fondazione COVID-19 Genomic Study (FOGS)\}",

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doi = "10.1038/s41588-025-02100-w",

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T1 - Genome-wide association study of long COVID

AU - Lammi, Vilma

AU - Nakanishi, Tomoko

AU - Jones, Samuel E.

AU - Andrews, Shea J.

AU - Fuentes-Guajardo, Macarena

AU - Fondazione COVID-19 Genomic Study (FOGS)

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/6

Y1 - 2025/6

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/105005985184

UR - https://pubmed.ncbi.nlm.nih.gov/40399555/

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DO - 10.1038/s41588-025-02100-w

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SN - 1061-4036

VL - 57

SP - 1402

EP - 1417

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Genome-wide association study of long COVID

Abstract

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