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Genome-wide association study of long COVID

Lammi V 1 , Nakanishi T 1 , Jones SE 1 , Andrews SJ 2 , Karjalainen J 1 , Cortés B 3 Show all authors , O'Brien HE 4 , Ochoa-Guzman A 5 , Fulton-Howard BE 6 , Broberg M 1 , Haapaniemi HH 1 , Kanai M 7 , Pirinen M 1 , Schmidt A 8 , Mitchell RE 9 , Mousas A 10 , Mangino M 11 , Huerta-Chagoya A 12 , Sinnott-Armstrong N 13 , Cirulli ET 14 , Vaudel M 15 , Kwong ASF 16 , Maiti AK 17 , Marttila MM 18 , Posner DC 19 , Rodriguez AA 20 , Batini C 21 , Minnai F 22 , Dearman AR 23 , Warmerdam CAR 24 , Sequeros CB 25 , Winkler TW 26 , Jordan DM 27 , Rešcenko R 28 , Miano L 29 , Lane JM 30 , Chung RK 31 , Guillen-Guio B 21 , Leavy OC 21 , Carvajal-Silva L 32 , Aguilar-Valdés K 32 , Frangione E 33 , Guare L 34 , Vergasova E 35 , Marouli E 36 , Striano P 37 , Zainulabid UA 38 , Kumar A 39 , Ahmad HF 40 , Edahiro R 41 , Azekawa S 42 , Long COVID Host Genetics Initiative , FinnGen , VA Million Veteran Program , MexGen-COVID Initiative , DBDS Genomic Consortium , GEN-COVID Multicenter Study , PHOSP-COVID Collaborative Group , GENCOV Study , Estonian Biobank Research Team , Luoh SW 43 , Erikstrup C 44 , Pedersen OBV 45 , Lerner-Ellis J 33 , Colombo A 32 , Grzymski JJ 46 , Ishii M 42 , Okada Y 47 , Beckmann ND 27 , Kumari M 23 , Wagner R 48 , Heid IM 26 , John C 21 , Short PJ 4 , Magnus P 49 , Ansone L 28 , Valenti LVC 50 , Lee SA 51 , Wain LV 21 , Verdugo RA 32 , Banasik K 25 , Geller F 52 , Franke LH 24 , Rakitko A 35 , Duncan EL 53 , Renieri A 54 , Tsilidis KK 10 , de Cid R 3 , Niavarani A 55 , Abner E 56 , Tusié-Luna T 57 , Verma SS 34 , Smith GD 9 , Timpson NJ 9 , Madduri RK 58 , Cho K 59 , Daly MJ 1 , Ganna A 1 , Schulte EC 60 , Richards JB 61 , Ludwig KU 8 , Marks-Hultström M 62 , Zeberg H 63 , Ollila HM 64

Affiliations 

  • 1 Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
  • 2 Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA
  • 3 Genomes for Life-GCAT Lab, CORE Program, Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
  • 4 Sano Genetics Limited, London, UK
  • 5 Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  • 6 Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
  • 7 Broad Institute, Cambridge, MA, USA
  • 8 Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany
  • 9 MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
  • 10 Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
  • 11 Department of Twin Research, King's College London, London, UK
  • 12 Program in Metabolism and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • 13 Herbold Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
  • 14 Helix, San Mateo, CA, USA
  • 15 Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway
  • 16 Centre for Clinical Brain Sciences, Division of Psychiatry, University of Edinburgh, Edinburgh, UK
  • 17 Department of Genetics and Genomics, Mydnavar, Southfield, MI, USA
  • 18 University of Helsinki, Helsinki, Finland
  • 19 VA Boston Healthcare System, Boston, MA, USA
  • 20 Data Science and Learning, Argonne National Laboratory, Lemont, IL, USA
  • 21 Department of Population Health Sciences, University of Leicester, Leicester, UK
  • 22 Institute for Biomedical Technologies-National Research Council, Segrate, Italy
  • 23 Institute for Social and Economic Research, University of Essex, Colchester, UK
  • 24 Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  • 25 Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 26 Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • 27 Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
  • 28 Latvian Biomedical Research and Study Centre, Riga, Latvia
  • 29 Università degli Studi di Milano, Milan, Italy
  • 30 Brigham and Women's Hospital Division of Sleep and Circadian Disorders, Boston, MA, USA
  • 31 Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA
  • 32 Departamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile
  • 33 Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
  • 34 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • 35 Genotek Ltd, Moscow, Russia
  • 36 William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  • 37 IRCCS G Gaslini, Genoa, Italy
  • 38 Department of Internal Medicine, Kulliyyah of Medicine, International Islamic University Malaysia, Pahang, Malaysia
  • 39 Department of Anatomy, All India Institute of Medical Sciences-Patna, Patna, India
  • 40 Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al Sultan Abdullah, Pahang, Malaysia
  • 41 Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
  • 42 Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
  • 43 VA Portland Health Care System, Portland, Portland, OR, USA
  • 44 Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
  • 45 Department of Clinical Immunology, Zealand University Hospital-Køge, Køge, Denmark
  • 46 Department of Internal Medicine, University of Nevada Reno, School of Medicine, Reno, NV, USA
  • 47 Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
  • 48 Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
  • 49 Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
  • 50 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
  • 51 Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, USA
  • 52 Statens Serum Institute, Copenhagen, Denmark
  • 53 Department of Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
  • 54 Medical Genetics, University of Siena, Siena, Italy
  • 55 Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • 56 Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
  • 57 Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
  • 58 Data Science and Learning Division, Argonne National Laboratory, Lemont, IL, USA
  • 59 Department of Medicine, Harvard Medical School and Mass General Brigham, Boston, MA, USA
  • 60 Department of Psychiatry, University of Munich, Munich, Germany
  • 61 Department of Human Genetics, McGill University, Montreal, Quebec, Canada
  • 62 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  • 63 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. hugo.zeberg@ki.se
  • 64 Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. hanna.m.ollila@helsinki.fi
Nat Genet, 2025 Jun;57(6):1402-1417.
PMID: 40399555 DOI: 10.1038/s41588-025-02100-w

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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