HE Long COVID project (Grant Agreement 101057553)
Published May 21, 2025 | Version v1
Journal article Open

Genome-wide association study of long COVID

Authors/Creators

  • 1. Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE)
  • 2. Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
  • 3. Department of Human Genetics, McGill University, Montreal, Quebec, Canada
  • 4. Centre for Clinical Epidemiology, Department of Medicine, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
  • 5. Kyoto-McGill International Collaborative Program in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • 6. Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
  • 7. Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan
  • 8. Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA
  • 9. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • 10. Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • 11. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
  • 12. Genomes for Life-GCAT Lab, CORE Program, Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
  • 13. Grup de REcerca en Impacte de les Malalties Cròniques i les seves Trajectòries (GRIMTra), Barcelona, Spain
  • 14. Sano Genetics Limited, London, UK
  • 15. Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  • 16. Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
  • 17. Broad Institute, Cambridge, MA, USA
  • 18. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • 19. Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
  • 20. Department of Public Health, University of Helsinki, Helsinki, Finland
  • 21. Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany
  • 22. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
  • 23. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • 24. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
  • 25. Department of Twin Research, King's College London, London, UK
  • 26. Program in Metabolism and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • 27. Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
  • 28. Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
  • 29. Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico
  • 30. Herbold Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
  • 31. Department of Genome Sciences, University of Washington, Seattle, WA, USA
  • 32. Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland
  • 33. Duke University
  • 34. Helix, San Mateo, CA, USA
  • 35. Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway
  • 36. Department of Genetics and Bioinformatics, Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway
  • 37. Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway
  • 38. Centre for Clinical Brain Sciences, Division of Psychiatry, University of Edinburgh, Edinburgh, UK
  • 39. Department of Genetics and Genomics, Mydnavar, Southfield, MI, USA
  • 40. University of Helsinki, Helsinki, Finland
  • 41. Helsinki University Central Hospital, Helsinki, Finland
  • 42. VA Boston Healthcare System, Boston, MA, USA
  • 43. Data Science and Learning, Argonne National Laboratory, Lemont, IL, USA
  • 44. Department of Population Health Sciences, University of Leicester, Leicester, UK
  • 45. University Hospitals of Leicester NHS Trust, Leicester, UK
  • 46. Institute for Biomedical Technologies—National Research Council, Segrate, Italy
  • 47. Department of Medical Biotechnology and Translational Medicine (BioMeTra), Università degli Studi di Milano, Milan, Italy
  • 48. Institute for Social and Economic Research, University of Essex, Colchester, UK
  • 49. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  • 50. Oncode Investigator, Utrecht, the Netherlands
  • 51. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 52. Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • 53. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
  • 54. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
  • 55. Latvian Biomedical Research and Study Centre, Riga, Latvia
  • 56. Università degli Studi di Milano, Milan, Italy
  • 57. Broad Institute
  • 58. Brigham and Women's Hospital Division of Sleep and Circadian Disorders, Boston, MA, USA
  • 59. Massachusetts General Hospital, Center for Genomic Medicine, Boston, MA, USA
  • 60. Broad Institute, Molecular and Population Genetics Program, Cambridge, MA, USA
  • 61. Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA
  • 62. The Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK
  • 63. Departamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile
  • 64. Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
  • 65. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • 66. Genotek Ltd, Moscow, Russia
  • 67. William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  • 68. IRCCS G Gaslini, Genoa, Italy
  • 69. Department of Internal Medicine, Kulliyyah of Medicine, International Islamic University Malaysia, Pahang, Malaysia
  • 70. Department of Anatomy, All India Institute of Medical Sciences—Patna, Patna, India
  • 71. Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al Sultan Abdullah, Pahang, Malaysia
  • 72. Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
  • 73. Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan
  • 74. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
  • 75. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 76. VA Portland Health Care System, Portland, Portland, OR, USA
  • 77. Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA
  • 78. Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
  • 79. Department of Clinical Immunology, Zealand University Hospital—Køge, Køge, Denmark
  • 80. University of Toronto, Toronto, Ontario, Canada
  • 81. Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada
  • 82. Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de Chile, Santiago, Chile
  • 83. Servicio de Anatomía Patológica, Hospital Clínico de la Universidad de Chile, Santiago, Chile
  • 84. University of Nevada, Reno
  • 85. Department of Internal Medicine, University of Nevada Reno, School of Medicine, Reno, NV, USA
  • 86. Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • 87. Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 88. Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan
  • 89. Division of Data Driven Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
  • 90. Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
  • 91. Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
  • 92. Leicester National Institute for Health and Care Research, Biomedical Research Centre, Glenfield Hospital, Leicester, UK
  • 93. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
  • 94. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
  • 95. Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  • 96. Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, USA
  • 97. Instituto de Investigación Interdisciplinaria y Facultad de Medicina, Universidad de Talca, Talca, Chile
  • 98. Hvidovre Hospital
  • 99. Statens Serum Institute, Copenhagen, Denmark
  • 100. Department of Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
  • 101. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
  • 102. Medical Genetics, University of Siena, Siena, Italy
  • 103. Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
  • 104. Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
  • 105. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  • 106. Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • 107. Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
  • 108. Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
  • 109. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  • 110. Argonne National Laboratory
  • 111. Data Science and Learning Division, Argonne National Laboratory, Lemont, IL, USA
  • 112. Department of Medicine, Harvard Medical School and Mass General Brigham, Boston, MA, USA
  • 113. University of Helsinki
  • 114. Department of Psychiatry, University of Munich, Munich, Germany
  • 115. Institute of Human Genetics, University Hospital, Faculty of Medicine, University of Bonn, Bonn, Germany
  • 116. Institute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany
  • 117. Institute of Psychiatric Phenomics and Genomics, University of Munich, Munich, Germany
  • 118. Department of Psychiatry, University Hospital, Faculty of Medicine, University of Bonn, Bonn, Germany
  • 119. 5 Prime Sciences Inc, Montreal, Quebec, Canada
  • 120. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  • 121. Lady Davis Institute of Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
  • 122. Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
  • 123. Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
  • 124. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
  • 125. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
  • 126. Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
  • 127. Broad Institute of MIT and Harvard, Cambridge, MA, USA

Description

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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Additional details

Funding

European Commission
Decision support for prediction and management of Long Covid Syndrome (LCS) 101057553

Dates

Submitted
2024-06-15
Accepted
2025-01-27
Available
2025-05-21

Software

Repository URL
https://www.nature.com/articles/s41588-025-02100-w