Genome-wide association study of long COVID

Long COVID Host Genetics Initiative; null FinnGen; Bonn Study of COVID Genetics (BoSCO); québécoise de la COVID-19 (BQC19) Banque; Longitudinal Study of Parents and Children (ALSPAC) Avon; VA Million Veteran Program; MexGen-COVID Initiative; Host Immune Response Pathogenesis Study (CHIRP) COVID-19; COVID-19 Genomics Network (C19-GenoNet); UnderstandingSociety: UK Household Longitudinal Study; Biobank (UKB) UK; null TwinsUK; Tirschenreuth Study (TiKoCo); Follow-UP study of patients with critical COVID-19 (SweCovid) and COVID-19 Cohort Study of the University Hospital of the Technical University Munich; Medicine BioBank (PMBB) Penn; Norwegian Mother Father and Child Cohort Study (MoBa); DBDS Genomic Consortium; Genomes for Life (GCAT) and Cohort COVID in Catalonia (COVICAT study); Environment and DNA (EXCEED) Extended Cohort for E-health; GEN-COVID Multicenter Study; Sinai COVID Biobank (MSCIC) Mount; null Lifelines; Japan COVID-19 Task Force; Genome-wide assessment of the gene variants associated with severe COVID-19 phenotype in Iran (IrCovid); Covid-19 Ioannina Biobank; Helix–Helix Exome+ and Healthy Nevada Project COVID-19 Phenotypes; null Genotek; of Long Covid (GOLD) Genetics; PHOSP-COVID collaborative group; GENCOV Study; (MGB) MassGeneralBrigham; Database of the Latvian Population (LGDB) Genome; Estonian Biobank Research Team; COVID-19 Genomic Study (FOGS) Fondazione; Vilma Lammi; Tomoko Nakanishi; Samuel E. Jones; Shea J. Andrews; Juha Karjalainen; Beatriz Cortés; Heath E. O’Brien; Ana Ochoa-Guzman; Brian E. Fulton-Howard; Martin Broberg; Hele H. 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; Minttu M. Marttila; Daniel C. Posner; Alexis A. Rodriguez; Chiara Batini; Francesca Minnai; Anna R. Dearman; C. A.Robert Warmerdam; Celia B. Sequeros; Thomas W. Winkler; Daniel M. Jordan; Raimonds Rešcenko; Lorenzo Miano; Jacqueline M. Lane; Ryan K. Chung; Beatriz Guillen-Guio; Olivia C. Leavy; Laura Carvajal-Silva; Kevin Aguilar-Valdés; Erika Frangione; Lindsay Guare; Ekaterina Vergasova; Eirini Marouli; Pasquale Striano; Ummu Afeera Zainulabid; Estefania Nova-Lamperti; Nicholas R. Harvey; Emma L. Duncan

doi:10.1038/s41588-025-02100-w

Genome-wide association study of long COVID

Long COVID Host Genetics Initiative (Group Author), FinnGen (Group Author), Bonn Study of COVID Genetics (BoSCO) (Group Author), québécoise de la COVID-19 (BQC19) Banque (Group Author), Longitudinal Study of Parents and Children (ALSPAC) Avon (Group Author), VA Million Veteran Program (Group Author), MexGen-COVID Initiative (Group Author), Host Immune Response Pathogenesis Study (CHIRP) COVID-19 (Group Author), COVID-19 Genomics Network (C19-GenoNet) (Group Author), UnderstandingSociety: UK Household Longitudinal Study (Group Author), Biobank (UKB) UK (Group Author), TwinsUK (Group Author), Tirschenreuth Study (TiKoCo) (Group Author), Follow-UP study of patients with critical COVID-19 (SweCovid) and COVID-19 Cohort Study of the University Hospital of the Technical University Munich (Group Author), Medicine BioBank (PMBB) Penn (Group Author), Norwegian Mother Father and Child Cohort Study (MoBa) (Group Author), DBDS Genomic Consortium (Group Author), Genomes for Life (GCAT) and Cohort COVID in Catalonia (COVICAT study) (Group Author), Environment and DNA (EXCEED) Extended Cohort for E-health (Group Author), GEN-COVID Multicenter Study (Group Author)Sinai COVID Biobank (MSCIC) Mount (Group Author), Lifelines (Group Author), Japan COVID-19 Task Force (Group Author), Genome-wide assessment of the gene variants associated with severe COVID-19 phenotype in Iran (IrCovid) (Group Author), Covid-19 Ioannina Biobank (Group Author), Helix–Helix Exome+ and Healthy Nevada Project COVID-19 Phenotypes (Group Author), Genotek (Group Author), of Long Covid (GOLD) Genetics (Group Author), PHOSP-COVID collaborative group (Group Author), GENCOV Study (Group Author), (MGB) MassGeneralBrigham (Group Author), Database of the Latvian Population (LGDB) Genome (Group Author), Estonian Biobank Research Team (Group Author), COVID-19 Genomic Study (FOGS) Fondazione (Group Author), Vilma Lammi, Tomoko Nakanishi, Samuel E. Jones, Shea J. Andrews, Juha Karjalainen, Beatriz Cortés, Heath E. O’Brien, Ana Ochoa-Guzman, Brian E. Fulton-Howard, Martin Broberg, Hele H. 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, Minttu M. Marttila, Daniel C. Posner, Alexis A. Rodriguez, Chiara Batini, Francesca Minnai, Anna R. Dearman, C. A.Robert Warmerdam, Celia B. Sequeros, Thomas W. Winkler, Daniel M. Jordan, Raimonds Rešcenko, Lorenzo Miano, Jacqueline M. Lane, Ryan K. Chung, Beatriz Guillen-Guio, Olivia C. Leavy, Laura Carvajal-Silva, Kevin Aguilar-Valdés, Erika Frangione, Lindsay Guare, Ekaterina Vergasova, Eirini Marouli, Pasquale Striano, Ummu Afeera Zainulabid, Estefania Nova-Lamperti, Nicholas R. Harvey, Emma L. Duncan

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

9 Citations (Scopus)

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.

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
Publication status	Published - 21 May 2025
Externally published	Yes

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10.1038/s41588-025-02100-wLicence: CC BY

Genome-wide association study of long COVIDFinal published version, 2.89 MBLicence: CC BY

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Initiative, L. COVID. H. G., FinnGen, (BoSCO), B. S. O. COVID. G., Banque, Q. D. L. COVID. BQC., Avon, L. S. O. P. A. C., Program, VA. M. V., Initiative, M.-COVID., COVID-19, H. I. R. P. S., (C19-GenoNet), COVID. G. N., Study, U. UK. H. L., UK, B., TwinsUK, (TiKoCo), T. S., Munich, F.-UP. S. O. P. W. C. COVID. A. COVID. C. S. O. T. U. H. O. T. T. U., Penn, M. B., (MoBa), N. M. F. A. C. C. S., Consortium, DBDS. G., study), G. F. L. A. C. COVID. I. C., Extended Cohort for E-health, E. A. DNA., ... Duncan, E. L. (2025). Genome-wide association study of long COVID. Nature Genetics, 57(6), 1402-1417. https://doi.org/10.1038/s41588-025-02100-w

@article{d755fd82d6fa47e49126f4aa709c8bb4,

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 = "Initiative, {Long COVID Host Genetics} and FinnGen and (BoSCO), {Bonn Study of COVID Genetics} and Banque, {qu{\'e}b{\'e}coise de la COVID-19 (BQC19)} and Avon, {Longitudinal Study of Parents and Children (ALSPAC)} and Program, {VA Million Veteran} and MexGen-COVID Initiative and COVID-19, {Host Immune Response Pathogenesis Study (CHIRP)} and (C19-GenoNet), {COVID-19 Genomics Network} and Study, {UnderstandingSociety: UK Household Longitudinal} and UK, {Biobank (UKB)} and TwinsUK and (TiKoCo), {Tirschenreuth Study} and Munich, {Follow-UP study of patients with critical COVID-19 (SweCovid) and COVID-19 Cohort Study of the University Hospital of the Technical University} and Penn, {Medicine BioBank (PMBB)} and (MoBa), {Norwegian Mother Father and Child Cohort Study} and Consortium, {DBDS Genomic} and study), {Genomes for Life (GCAT) and Cohort COVID in Catalonia (COVICAT} and {Extended Cohort for E-health}, {Environment and DNA (EXCEED)} and Study, {GEN-COVID Multicenter} and Mount, {Sinai COVID Biobank (MSCIC)} and Lifelines and Force, {Japan COVID-19 Task} and (IrCovid), {Genome-wide assessment of the gene variants associated with severe COVID-19 phenotype in Iran} and Biobank, {Covid-19 Ioannina} and Phenotypes, {Helix–Helix Exome+ and Healthy Nevada Project COVID-19} and Genotek and Genetics, {of Long Covid (GOLD)} and group, {PHOSP-COVID collaborative} and GENCOV Study and (MGB) MassGeneralBrigham and Genome, {Database of the Latvian Population (LGDB)} and Team, {Estonian Biobank Research} and Fondazione, {COVID-19 Genomic Study (FOGS)} and Vilma Lammi and Tomoko Nakanishi and Jones, {Samuel E.} and Andrews, {Shea J.} and Juha Karjalainen and Beatriz Cort{\'e}s and O{\textquoteright}Brien, {Heath E.} and Ana Ochoa-Guzman and Fulton-Howard, {Brian E.} and Martin Broberg and Haapaniemi, {Hele H.} and Masahiro Kanai and Matti Pirinen and Axel Schmidt and Mitchell, {Ruth E.} and Abdou Mousas and Massimo Mangino and Alicia Huerta-Chagoya and Nasa Sinnott-Armstrong and Cirulli, {Elizabeth T.} and Marc Vaudel and Kwong, {Alex S.F.} and Maiti, {Amit K.} and Marttila, {Minttu M.} and Posner, {Daniel C.} and Rodriguez, {Alexis A.} and Chiara Batini and Francesca Minnai and Dearman, {Anna R.} and Warmerdam, {C. A.Robert} and Sequeros, {Celia B.} and Winkler, {Thomas W.} and Jordan, {Daniel M.} and Raimonds Re{\v s}cenko and Lorenzo Miano and Lane, {Jacqueline M.} and Chung, {Ryan K.} and Beatriz Guillen-Guio and Leavy, {Olivia C.} and Laura Carvajal-Silva and Kevin Aguilar-Vald{\'e}s and Erika Frangione and Lindsay Guare and Ekaterina Vergasova and Eirini Marouli and Pasquale Striano and Zainulabid, {Ummu Afeera} and Estefania Nova-Lamperti and Harvey, {Nicholas R.} and Duncan, {Emma L.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = may,

day = "21",

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

language = "English",

volume = "57",

pages = "1402--1417",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

Initiative, LCOVIDHG, FinnGen, (BoSCO), BSOCOVIDG, Banque, QDLCOVIDBQC, Avon, LSOPAC, Program, VAMV, Initiative, M-COVID, COVID-19, HIRPS, (C19-GenoNet), COVIDGN, Study, UUKHL, UK, B, TwinsUK, (TiKoCo), TS, Munich, F-UPSOPWCCOVIDACOVIDCSOTUHOTTU, Penn, MB, (MoBa), NMFACCS, Consortium, DBDSG, study), GFLACCOVIDIC, Extended Cohort for E-health, EADNA, Study, GEN-COVIDM, Mount, SCOVIDB, Lifelines, Force, JCOVIDT, (IrCovid), GAOTGVAWSCOVIDPII, Biobank, CI, Phenotypes, HHEAHNPCOVID, Genotek, Genetics, OLC, group, PHOSP-COVIDC, Study, GENCOV, MassGeneralBrigham, Genome, DOTLP, Team, EBR, Fondazione, COVIDGS, Lammi, V, Nakanishi, T, Jones, SE, Andrews, SJ, Karjalainen, J, Cortés, B, O’Brien, HE, Ochoa-Guzman, A, Fulton-Howard, BE, Broberg, M, Haapaniemi, HH, Kanai, M, Pirinen, M, Schmidt, A, Mitchell, RE, Mousas, A, Mangino, M, Huerta-Chagoya, A, Sinnott-Armstrong, N, Cirulli, ET, Vaudel, M, Kwong, ASF, Maiti, AK, Marttila, MM, Posner, DC, Rodriguez, AA, Batini, C, Minnai, F, Dearman, AR, Warmerdam, CAR, Sequeros, CB, Winkler, TW, Jordan, DM, Rešcenko, R, Miano, L, Lane, JM, Chung, RK, Guillen-Guio, B, Leavy, OC, Carvajal-Silva, L, Aguilar-Valdés, K, Frangione, E, Guare, L, Vergasova, E, Marouli, E, Striano, P, Zainulabid, UA, Nova-Lamperti, E, Harvey, NR & Duncan, EL 2025, 'Genome-wide association study of long COVID', Nature Genetics, vol. 57, no. 6, pp. 1402-1417. https://doi.org/10.1038/s41588-025-02100-w

TY - JOUR

T1 - Genome-wide association study of long COVID

AU - Initiative, Long COVID Host Genetics

AU - FinnGen, null

AU - (BoSCO), Bonn Study of COVID Genetics

AU - Banque, québécoise de la COVID-19 (BQC19)

AU - Avon, Longitudinal Study of Parents and Children (ALSPAC)

AU - Program, VA Million Veteran

AU - Initiative, MexGen-COVID

AU - COVID-19, Host Immune Response Pathogenesis Study (CHIRP)

AU - (C19-GenoNet), COVID-19 Genomics Network

AU - Study, UnderstandingSociety: UK Household Longitudinal

AU - UK, Biobank (UKB)

AU - TwinsUK, null

AU - (TiKoCo), Tirschenreuth Study

AU - Munich, Follow-UP study of patients with critical COVID-19 (SweCovid) and COVID-19 Cohort Study of the University Hospital of the Technical University

AU - Penn, Medicine BioBank (PMBB)

AU - (MoBa), Norwegian Mother Father and Child Cohort Study

AU - Consortium, DBDS Genomic

AU - study), Genomes for Life (GCAT) and Cohort COVID in Catalonia (COVICAT

AU - Extended Cohort for E-health, Environment and DNA (EXCEED)

AU - Study, GEN-COVID Multicenter

AU - Mount, Sinai COVID Biobank (MSCIC)

AU - Lifelines, null

AU - Force, Japan COVID-19 Task

AU - (IrCovid), Genome-wide assessment of the gene variants associated with severe COVID-19 phenotype in Iran

AU - Biobank, Covid-19 Ioannina

AU - Phenotypes, Helix–Helix Exome+ and Healthy Nevada Project COVID-19

AU - Genotek, null

AU - Genetics, of Long Covid (GOLD)

AU - group, PHOSP-COVID collaborative

AU - Study, GENCOV

AU - MassGeneralBrigham, (MGB)

AU - Genome, Database of the Latvian Population (LGDB)

AU - Team, Estonian Biobank Research

AU - Fondazione, COVID-19 Genomic Study (FOGS)

AU - Lammi, Vilma

AU - Nakanishi, Tomoko

AU - Jones, Samuel E.

AU - Andrews, Shea J.

AU - Karjalainen, Juha

AU - Cortés, Beatriz

AU - O’Brien, Heath E.

AU - Ochoa-Guzman, Ana

AU - Fulton-Howard, Brian E.

AU - Broberg, Martin

AU - Haapaniemi, Hele H.

AU - Kanai, Masahiro

AU - Pirinen, Matti

AU - Schmidt, Axel

AU - Mitchell, Ruth E.

AU - Mousas, Abdou

AU - Mangino, Massimo

AU - Huerta-Chagoya, Alicia

AU - Sinnott-Armstrong, Nasa

AU - Cirulli, Elizabeth T.

AU - Vaudel, Marc

AU - Kwong, Alex S.F.

AU - Maiti, Amit K.

AU - Marttila, Minttu M.

AU - Posner, Daniel C.

AU - Rodriguez, Alexis A.

AU - Batini, Chiara

AU - Minnai, Francesca

AU - Dearman, Anna R.

AU - Warmerdam, C. A.Robert

AU - Sequeros, Celia B.

AU - Winkler, Thomas W.

AU - Jordan, Daniel M.

AU - Rešcenko, Raimonds

AU - Miano, Lorenzo

AU - Lane, Jacqueline M.

AU - Chung, Ryan K.

AU - Guillen-Guio, Beatriz

AU - Leavy, Olivia C.

AU - Carvajal-Silva, Laura

AU - Aguilar-Valdés, Kevin

AU - Frangione, Erika

AU - Guare, Lindsay

AU - Vergasova, Ekaterina

AU - Marouli, Eirini

AU - Striano, Pasquale

AU - Zainulabid, Ummu Afeera

AU - Nova-Lamperti, Estefania

AU - Harvey, Nicholas R.

AU - Duncan, Emma L.

PY - 2025/5/21

Y1 - 2025/5/21

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 - http://www.scopus.com/inward/record.url?scp=105005985184&partnerID=8YFLogxK

U2 - 10.1038/s41588-025-02100-w

DO - 10.1038/s41588-025-02100-w

M3 - Article

C2 - 40399555

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

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