Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall
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.
Authors
- Raquel Cruz (ORCID: https://orcid.org/0000-0002-6964-8898)
- Ramón Brugada (ORCID: https://orcid.org/0000-0001-6607-3032)
- Héctor Cubero-Gallego (ORCID: https://orcid.org/0000-0001-9740-827X)
- Mel·lina Pinsach‐Abuin (ORCID: https://orcid.org/0000-0001-7199-512X)
- Irene R. Dégano (ORCID: https://orcid.org/0000-0003-1914-6934)
- Ruth Martí‐Lluch (ORCID: https://orcid.org/0000-0002-7320-9521)
- Silvia Diz‐de Almeida (ORCID: https://orcid.org/0000-0003-2813-8928)
- Alexandra Pérez-Serra (ORCID: https://orcid.org/0000-0001-5344-6573)
- Robert Güerri‐Fernández (ORCID: https://orcid.org/0000-0002-9794-9161)
- Joan Ramón Masclans (ORCID: https://orcid.org/0000-0002-0809-6823)
- Marta Puigmulé (ORCID: https://orcid.org/0000-0001-7881-8839)
- Beatriz Vaquerizo (ORCID: https://orcid.org/0000-0002-1428-3596)
- Rafel Ramos (ORCID: https://orcid.org/0000-0001-7970-5537)
- Álvaro Hernáez (ORCID: https://orcid.org/0000-0001-8593-1477)
- Xavier Nogués (ORCID: https://orcid.org/0000-0002-5537-1859)
- Anna Camps (ORCID: https://orcid.org/0000-0001-9644-8421)
- Helena Tizón‐Marcos (ORCID: https://orcid.org/0000-0001-7942-9413)
- Jaume Marrugat (ORCID: https://orcid.org/0000-0003-3320-554X)
- Elisabet Selga (ORCID: https://orcid.org/0000-0002-4290-8370)
- Roberto Elosúa (ORCID: https://orcid.org/0000-0001-8235-0095)
- Sara Polo-Alonso
- Isaac Subirana
- Eulàlia Puigdecant
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Universitat Autònoma de Barcelona (ES)
- Universitat Pompeu Fabra (ES)
- Universidade de Santiago de Compostela (ES)
- Universitat de Girona (ES)
- Instituto de Salud Carlos III (ES)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Center for Research in Molecular Medicine and Chronic Diseases (ES)
- Institut d'Investigació Biomèdica de Girona (ES)
- Centro de Investigación Biomédica en Red (ES)
- Institut Universitari d'Investigació en Atenció Primària Jordi Gol (ES)
- Hospital Del Mar (ES)
- Primary Health Care (QA)
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES)
- Hospital Universitari de Girona Doctor Josep Trueta (ES)
- Instituto de Investigación de Enfermedades Raras (ES)
- Universitat Ramon Llull (ES)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-09-22
- DOI
- https://doi.org/10.3390/ijms26189252
- Primary Topic
- Long-Term Effects of COVID-19
- Type
- article
- Field-Weighted Citation Impact
- 0.00