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Genome-wide association study of long COVID
Vilma Lammi1, Tomoko Nakanishi1,2,3,4,5,6, Samuel E Jones1
1Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Nature Genetics
|May 21, 2025
Summary
A genome-wide study found a link between the FOXP4 gene and long COVID, a persistent condition after SARS-CoV-2 infection. This suggests lung function plays a key role in developing long COVID symptoms.
Area of Science:
- Genetics
- Infectious Diseases
- Pulmonology
Background:
- Infections can cause persistent symptoms, like shingles after varicella zoster or rheumatic fever after streptococcal infections.
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to long COVID, characterized by fatigue, pulmonary issues, and cognitive dysfunction.
- The biological mechanisms underlying long COVID are not yet understood.
Purpose of the Study:
- To investigate the genetic underpinnings of long COVID.
- To identify genetic associations with the risk of developing long COVID.
Main Methods:
- A large-scale genome-wide association study (GWAS) was conducted.
- The study included up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries.
- Replication analysis was performed using 9,500 long COVID cases and 798,835 population controls.
Main Results:
- A significant association was discovered between the FOXP4 gene and long COVID.
- This association was independent of FOXP4's previously known link to severe COVID-19.
- The FOXP4 association with long COVID was successfully replicated in a larger, independent cohort.
Conclusions:
- The FOXP4 gene is implicated in the pathophysiology of long COVID.
- FOXP4's known role in lung physiology and pathology suggests that lung function is crucial in the development of long COVID.
- Further research into FOXP4 and lung function may elucidate long COVID mechanisms.
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