Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany
Abstract If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying p...
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2025-05-01
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| author | Anne-Kathrin Ruß Stefan Schreiber Wolfgang Lieb J. Janne Vehreschild Peter U. Heuschmann Thomas Illig Katharina S. Appel Maria J. G. T. Vehreschild Dagmar Krefting Lennart Reinke Alin Viebke Susanne Poick Stefan Störk Jens-Peter Reese Thomas Zoller Lilian Krist David Ellinghaus Bärbel U. Foesel Christian Gieger Bettina Lorenz-Depiereux Martin Witzenrath Gabriele Anton Michael Krawczak Jan Heyckendorf Thomas Bahmer |
| author_facet | Anne-Kathrin Ruß Stefan Schreiber Wolfgang Lieb J. Janne Vehreschild Peter U. Heuschmann Thomas Illig Katharina S. Appel Maria J. G. T. Vehreschild Dagmar Krefting Lennart Reinke Alin Viebke Susanne Poick Stefan Störk Jens-Peter Reese Thomas Zoller Lilian Krist David Ellinghaus Bärbel U. Foesel Christian Gieger Bettina Lorenz-Depiereux Martin Witzenrath Gabriele Anton Michael Krawczak Jan Heyckendorf Thomas Bahmer |
| author_sort | Anne-Kathrin Ruß |
| collection | DOAJ |
| description | Abstract If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying potential genetic modifiers of PCS remains of great clinical and scientific interest. We therefore performed a case-control type genome-wide association study (GWAS) of three recently developed PCS (severity) scores in 2,247 participants of COVIDOM, a prospective, multi-centre, population-based cohort study of SARS-CoV-2-infected individuals in Germany. Each PCS score originally represented the weighted sum of the binary indicators of all, or a subset, of 12 PCS symptom complexes, assessed six months or later after the PCR test-confirmed SARS-CoV-2 infection of a participant. For various methodical reasons, however, the PCS scores were dichotomized along their respective median values in the present study, prior to the GWAS. Of the 6,383,167 single nucleotide polymorphisms included, various variants were found to be associated with at least one of the PCS scores, although not at the stringent genome-wide statistical significance level of 5 × 10− 8. With p = 6.6 × 10− 8, however, the genotype-phenotype association of SNP rs9792535 at position chr9:127,166,653 narrowly missed this threshold. The SNP is located in a region including the NEK6, PSMB7 and ADGRD2 genes which, however, does not immediately suggest an etiological connection to PCS. As regards functional plausibility, variants of a possible effect mapped to the olfactory receptor gene region (lead SNP rs10893121 at position chr11:123,854,744; p = 2.5 × 10− 6). Impairment of smell and taste is a pathognomonic feature of both, acute COVID-19 and PCS, and our results suggest that this connection may have a genetic basis. Three other genotype-phenotype associations pointed towards a possible etiological role in PCS of cellular virus repression (CHD6 gene region), activation of macrophages (SLC7A2) and the release of virus particles from infected cells (ARHGAP44). All other gene regions highlighted by our GWAS did not relate to pathophysiological processes currently discussed for PCS. Therefore, and because the genotype-phenotype associations observed in our GWAS were generally not very strong, the complexity of the genetic background of PCS appears to be as high as that of most other multifactorial traits in humans. |
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| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-835d10145a024da8aeb202b33e05986e2025-08-20T03:09:19ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-00945-zGenome-wide association study of post COVID-19 syndrome in a population-based cohort in GermanyAnne-Kathrin Ruß0Stefan Schreiber1Wolfgang Lieb2J. Janne Vehreschild3Peter U. Heuschmann4Thomas Illig5Katharina S. Appel6Maria J. G. T. Vehreschild7Dagmar Krefting8Lennart Reinke9Alin Viebke10Susanne Poick11Stefan Störk12Jens-Peter Reese13Thomas Zoller14Lilian Krist15David Ellinghaus16Bärbel U. Foesel17Christian Gieger18Bettina Lorenz-Depiereux19Martin Witzenrath20Gabriele Anton21Michael Krawczak22Jan Heyckendorf23Thomas Bahmer24Institute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Kiel UniversityDepartment of Internal Medicine I, University Medical Center Schleswig-HolsteinInstitute of Epidemiology, University Medical Center Schleswig-Holstein, Kiel UniversityInstitute of Digital Medicine and Clinical Data Science, Faculty of Medicine, Goethe University FrankfurtInstitute of Clinical Epidemiology and Biometry, University of WürzburgHannover Unified Biobank, Hannover Medical SchoolInstitute of Digital Medicine and Clinical Data Science, Faculty of Medicine, Goethe University FrankfurtMedical Department 2, Center for Internal Medicine, University Hospital Frankfurt, Goethe University FrankfurtDepartment of Medical Informatics, University Medical Center GöttingenDepartment of Internal Medicine I, University Medical Center Schleswig-HolsteinDepartment of Internal Medicine I, University Medical Center Schleswig-HolsteinInstitute of Epidemiology, University Medical Center Schleswig-Holstein, Kiel UniversityDepartment of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, University Hospital WürzburgInstitute of Clinical Epidemiology and Biometry, University of WürzburgDepartment of Infectious Diseases, Respiratory and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu BerlinInstitute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu BerlinInstitute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Kiel UniversityInstitute of Epidemiology, Research Unit of Molecular Epidemiology, Helmholtz Munich - German Research Center for Environmental HealthInstitute of Epidemiology, Research Unit of Molecular Epidemiology, Helmholtz Munich - German Research Center for Environmental HealthInstitute of Epidemiology, Research Unit of Molecular Epidemiology, Helmholtz Munich - German Research Center for Environmental HealthDepartment of Infectious Diseases and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu BerlinMedical School OWL, Bielefeld UniversityInstitute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Kiel UniversityDepartment of Internal Medicine I, University Medical Center Schleswig-HolsteinDepartment of Internal Medicine I, University Medical Center Schleswig-HolsteinAbstract If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying potential genetic modifiers of PCS remains of great clinical and scientific interest. We therefore performed a case-control type genome-wide association study (GWAS) of three recently developed PCS (severity) scores in 2,247 participants of COVIDOM, a prospective, multi-centre, population-based cohort study of SARS-CoV-2-infected individuals in Germany. Each PCS score originally represented the weighted sum of the binary indicators of all, or a subset, of 12 PCS symptom complexes, assessed six months or later after the PCR test-confirmed SARS-CoV-2 infection of a participant. For various methodical reasons, however, the PCS scores were dichotomized along their respective median values in the present study, prior to the GWAS. Of the 6,383,167 single nucleotide polymorphisms included, various variants were found to be associated with at least one of the PCS scores, although not at the stringent genome-wide statistical significance level of 5 × 10− 8. With p = 6.6 × 10− 8, however, the genotype-phenotype association of SNP rs9792535 at position chr9:127,166,653 narrowly missed this threshold. The SNP is located in a region including the NEK6, PSMB7 and ADGRD2 genes which, however, does not immediately suggest an etiological connection to PCS. As regards functional plausibility, variants of a possible effect mapped to the olfactory receptor gene region (lead SNP rs10893121 at position chr11:123,854,744; p = 2.5 × 10− 6). Impairment of smell and taste is a pathognomonic feature of both, acute COVID-19 and PCS, and our results suggest that this connection may have a genetic basis. Three other genotype-phenotype associations pointed towards a possible etiological role in PCS of cellular virus repression (CHD6 gene region), activation of macrophages (SLC7A2) and the release of virus particles from infected cells (ARHGAP44). All other gene regions highlighted by our GWAS did not relate to pathophysiological processes currently discussed for PCS. Therefore, and because the genotype-phenotype associations observed in our GWAS were generally not very strong, the complexity of the genetic background of PCS appears to be as high as that of most other multifactorial traits in humans.https://doi.org/10.1038/s41598-025-00945-zSARS-CoV-2Long-COVIDGenotype-phenotype associationLinkage disequilibriumSingle nucleotide polymorphismOlfactory receptor |
| spellingShingle | Anne-Kathrin Ruß Stefan Schreiber Wolfgang Lieb J. Janne Vehreschild Peter U. Heuschmann Thomas Illig Katharina S. Appel Maria J. G. T. Vehreschild Dagmar Krefting Lennart Reinke Alin Viebke Susanne Poick Stefan Störk Jens-Peter Reese Thomas Zoller Lilian Krist David Ellinghaus Bärbel U. Foesel Christian Gieger Bettina Lorenz-Depiereux Martin Witzenrath Gabriele Anton Michael Krawczak Jan Heyckendorf Thomas Bahmer Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany Scientific Reports SARS-CoV-2 Long-COVID Genotype-phenotype association Linkage disequilibrium Single nucleotide polymorphism Olfactory receptor |
| title | Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany |
| title_full | Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany |
| title_fullStr | Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany |
| title_full_unstemmed | Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany |
| title_short | Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany |
| title_sort | genome wide association study of post covid 19 syndrome in a population based cohort in germany |
| topic | SARS-CoV-2 Long-COVID Genotype-phenotype association Linkage disequilibrium Single nucleotide polymorphism Olfactory receptor |
| url | https://doi.org/10.1038/s41598-025-00945-z |
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