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.
Author affiliation
College of Life Sciences
Population Health SciencesPublished in
Nature GeneticsVolume
57Pagination
1402-1417Publisher
Springer Science and Business Media LLCissn
1061-4036eissn
1546-1718Copyright date
2025Available date
2025-06-30Spatial coverage
United StatesLanguage
enDeposited by
Dr Chiara BatiniDeposit date
2025-05-30Data Access Statement
We have made the results of these GWAS meta-analyses publicly available for variants passing post-meta-analysis filtering for MAF ≥ 1% and effective sample size >1/3 of the maximum effective sample size for each meta-analysis. The results from the four meta-analyses have been deposited to GWAS Catalog67 and LocusZoom68, where the associations can be visually explored and the summary statistics exported for further scientific discovery.
Strict case definition (long COVID after test-verified SARS-CoV-2 infection) versus broad control definition (population control):
https://www.ebi.ac.uk/gwas/studies/GCST90454540
https://my.locuszoom.org/gwas/192226/
Broad case definition (long COVID after any SARS-CoV-2 infection) versus broad control definition:
https://www.ebi.ac.uk/gwas/studies/GCST90454541
https://my.locuszoom.org/gwas/826733/
Strict case definition versus strict control definition (individuals that had SARS-CoV-2 but did not develop long COVID):
https://www.ebi.ac.uk/gwas/studies/GCST90454542
https://my.locuszoom.org/gwas/793752/
Broad case definition versus strict control definition:
https://www.ebi.ac.uk/gwas/studies/GCST90454543
https://my.locuszoom.org/gwas/91854/