Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis
Abstract This study uses Mendelian randomization (MR) to investigate the potential causal relationships between viral infections, including Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), SARS-CoV-2, cytomegalovirus (CMV), human herpes virus 6 (HHV-6), varicella-zoster virus (VZV), her...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-08361-z |
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| author | Ting Cheng He-Yi Zhang Tian-Run Wang Ruo-Lan Li Zhi-Nan Jing Yue-Hong Huo Sheng-Xiao Zhang |
| author_facet | Ting Cheng He-Yi Zhang Tian-Run Wang Ruo-Lan Li Zhi-Nan Jing Yue-Hong Huo Sheng-Xiao Zhang |
| author_sort | Ting Cheng |
| collection | DOAJ |
| description | Abstract This study uses Mendelian randomization (MR) to investigate the potential causal relationships between viral infections, including Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), SARS-CoV-2, cytomegalovirus (CMV), human herpes virus 6 (HHV-6), varicella-zoster virus (VZV), herpes simplex virus (HSV), influenza A virus, and hepatitis B virus, and the risk of systemic sclerosis (SSc). Summary-level data on viral exposures and SSc outcomes were obtained from public genome-wide association studies (GWAS) databases. Causality was assessed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analysis was conducted to enhance the reliability and robustness of our findings. Genetically predicted anti-EBV viral capsid antigen IgG levels (OR = 3.400, 95% CI = 1.093–10.571, p = 0.035) were causally associated with an elevated risk of SSc, while HIV (OR = 0.787, 95% CI = 0.629–0.985, p = 0.037) and SARS-CoV-2 (OR = 0.335, 95% CI = 0.116–0.964, p = 0.043) correlated with a reduced risk of SSc. Sensitivity analysis validated the robustness of these associations (p > 0.05). Further elucidation of the underlying mechanisms by which EBV increases the risk of SSc could potentially identify interventions for promoting SSc prevention. |
| format | Article |
| id | doaj-art-8c52dae92e3f4aa18dde5869be09b627 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-8c52dae92e3f4aa18dde5869be09b6272025-08-20T03:38:15ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-08361-zMendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosisTing Cheng0He-Yi Zhang1Tian-Run Wang2Ruo-Lan Li3Zhi-Nan Jing4Yue-Hong Huo5Sheng-Xiao Zhang6Department of Rheumatology, the Second Hospital of Shanxi Medical UniversityShanxi Provincial Key Laboratory of Rheumatism Immune MicroecologyShanxi Provincial Key Laboratory of Rheumatism Immune MicroecologyShanxi Provincial Key Laboratory of Rheumatism Immune MicroecologyShanxi Provincial Key Laboratory of Rheumatism Immune MicroecologyShanxi Provincial Key Laboratory of Rheumatism Immune MicroecologyDepartment of Rheumatology, the Second Hospital of Shanxi Medical UniversityAbstract This study uses Mendelian randomization (MR) to investigate the potential causal relationships between viral infections, including Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), SARS-CoV-2, cytomegalovirus (CMV), human herpes virus 6 (HHV-6), varicella-zoster virus (VZV), herpes simplex virus (HSV), influenza A virus, and hepatitis B virus, and the risk of systemic sclerosis (SSc). Summary-level data on viral exposures and SSc outcomes were obtained from public genome-wide association studies (GWAS) databases. Causality was assessed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analysis was conducted to enhance the reliability and robustness of our findings. Genetically predicted anti-EBV viral capsid antigen IgG levels (OR = 3.400, 95% CI = 1.093–10.571, p = 0.035) were causally associated with an elevated risk of SSc, while HIV (OR = 0.787, 95% CI = 0.629–0.985, p = 0.037) and SARS-CoV-2 (OR = 0.335, 95% CI = 0.116–0.964, p = 0.043) correlated with a reduced risk of SSc. Sensitivity analysis validated the robustness of these associations (p > 0.05). Further elucidation of the underlying mechanisms by which EBV increases the risk of SSc could potentially identify interventions for promoting SSc prevention.https://doi.org/10.1038/s41598-025-08361-zVirus infectionSystemic sclerosisMendelian randomizationCausal relationshipGenome-wide association study |
| spellingShingle | Ting Cheng He-Yi Zhang Tian-Run Wang Ruo-Lan Li Zhi-Nan Jing Yue-Hong Huo Sheng-Xiao Zhang Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis Scientific Reports Virus infection Systemic sclerosis Mendelian randomization Causal relationship Genome-wide association study |
| title | Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis |
| title_full | Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis |
| title_fullStr | Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis |
| title_full_unstemmed | Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis |
| title_short | Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis |
| title_sort | mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis |
| topic | Virus infection Systemic sclerosis Mendelian randomization Causal relationship Genome-wide association study |
| url | https://doi.org/10.1038/s41598-025-08361-z |
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