TY - JOUR
T1 - Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall
AU - Polo-Alonso, Sara
AU - Hernáez, Álvaro
AU - Dégano, Irene R.
AU - Martí-Lluch, Ruth
AU - Pinsach-Abuin, Mel·lina
AU - Elosua, Roberto
AU - Subirana, Isaac
AU - Puigmulé, Marta
AU - Pérez, Alexandra
AU - Cruz, Raquel
AU - Diz-de Almeida, Silvia
AU - Puigdecant, Eulàlia
AU - Selga, Elisabet
AU - Nogues, Xavier
AU - Masclans, Joan Ramon
AU - Güerri-Fernández, Roberto
AU - Cubero-Gallego, Héctor
AU - Tizon-Marcos, Helena
AU - Vaquerizo, Beatriz
AU - Brugada, Ramon
AU - Ramos, Rafel
AU - Camps-Vilaró, Anna
AU - Marrugat, Jaume
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/9
Y1 - 2025/9
N2 - We aimed to explore the global and sex-specific genetic variants associated with long COVID, as defined by patient-driven symptom recall. A 1-year cohort study of 2411 COVID-19 patients collected long COVID symptoms with an open-ended, non-directed questionnaire, and long COVID incidence was determined according to the World Health Organization definition. Global and sex-stratified genome-wide association analyses were conducted by logistic regression models adjusted for age, sex (in the global analysis), and the first 10 principal components. We assessed sex-variant interactions and performed gene-based analyses, gene mapping, and gene-set enrichment analyses. When comparing the 1392 long COVID cases with the non-cases, we identified 23 lead variants from suggestive signals: 13 from the global analysis, 5 from females, and 5 from males. Five variants showed a significant interaction with sex (two in females, three in males). We mapped 15 protein-coding genes related to diseases of the immune and nervous systems and tumoral processes. Notably, CD5 and VPS37C, linked to immune function, were significantly associated with long COVID in men. Our results suggest that persistent immune dysregulation may be involved in the development of precisely defined long COVID.
AB - We aimed to explore the global and sex-specific genetic variants associated with long COVID, as defined by patient-driven symptom recall. A 1-year cohort study of 2411 COVID-19 patients collected long COVID symptoms with an open-ended, non-directed questionnaire, and long COVID incidence was determined according to the World Health Organization definition. Global and sex-stratified genome-wide association analyses were conducted by logistic regression models adjusted for age, sex (in the global analysis), and the first 10 principal components. We assessed sex-variant interactions and performed gene-based analyses, gene mapping, and gene-set enrichment analyses. When comparing the 1392 long COVID cases with the non-cases, we identified 23 lead variants from suggestive signals: 13 from the global analysis, 5 from females, and 5 from males. Five variants showed a significant interaction with sex (two in females, three in males). We mapped 15 protein-coding genes related to diseases of the immune and nervous systems and tumoral processes. Notably, CD5 and VPS37C, linked to immune function, were significantly associated with long COVID in men. Our results suggest that persistent immune dysregulation may be involved in the development of precisely defined long COVID.
KW - COVID-19
KW - genetic polymorphism
KW - genome-wide association study
KW - post-acute COVID-19 syndrome
KW - SARS-CoV-2
KW - sex characteristics
UR - https://www.scopus.com/pages/publications/105017415351
U2 - 10.3390/ijms26189252
DO - 10.3390/ijms26189252
M3 - Article
C2 - 41009814
AN - SCOPUS:105017415351
SN - 1661-6596
VL - 26
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 18
M1 - 9252
ER -