Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization study
Abstract Background It is well-documented that systemic lupus erythematosus (SLE) is associated with asthma. However, the causal relationship between SLE and asthma, and the potential mediator need to be explained. This study aims to confirm the cause-and-effect relationship between SLE and asthma,...
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BMC
2025-07-01
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| Series: | BMC Rheumatology |
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| Online Access: | https://doi.org/10.1186/s41927-025-00539-2 |
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| author | Hui Yin Tongxia Wang Lin Liu Zhi Hu |
| author_facet | Hui Yin Tongxia Wang Lin Liu Zhi Hu |
| author_sort | Hui Yin |
| collection | DOAJ |
| description | Abstract Background It is well-documented that systemic lupus erythematosus (SLE) is associated with asthma. However, the causal relationship between SLE and asthma, and the potential mediator need to be explained. This study aims to confirm the cause-and-effect relationship between SLE and asthma, and evaluate the mediation effect of lipid in European ancestry. Methods A Two-sample Mendelian randomization (MR) study was applied to analyze the causal relationships between SLE and asthma. A two-step MR design was used to explore whether low-density lipoprotein cholesterol (LDL-C) mediates the causal pathway from SLE to asthma outcome. Cochran’s Q statistic methods and MR-Egger regression were used to assess heterogeneity and pleiotropy. Leave-one-out (LOO) sensitivity test was adopted to estimate the effect of removing one of the selected individual SNPs on the overall results. Funnel and forest plots were also conducted to detect the pleiotropy directly. Results SLE was significantly associated with higher asthma risk according to inverse-variance weighted (IVW) method [OR (95%CI): 1.093 (1.024–1.166)] (P = 0.007), MR Egger method [OR (95%CI): 1.192 (1.077–1.319)] (P = 0.028) and Maximum likelihood [OR (95%CI): 1.094 (1.036–1.155)] (P = 0.001), which were robust across adequate sensitivity analysis. On the contrary, asthma has no causal relationship with SLE. In addition, LDL-C may mediate a proportion of 6.15% of the total effect between SLE and asthma. Conclusion This study demonstrates that patients with SLE may have a higher risk of developing asthma, which may be mediated by LDL-C. Understanding this relationship provides insight into potential mechanisms underlying asthma development in SLE patients and offers a foundation for developing targeted treatment strategies to manage these risks effectively. |
| format | Article |
| id | doaj-art-6f2f9928cf7545319afbc7e9fd6902a1 |
| institution | Kabale University |
| issn | 2520-1026 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Rheumatology |
| spelling | doaj-art-6f2f9928cf7545319afbc7e9fd6902a12025-08-20T04:02:45ZengBMCBMC Rheumatology2520-10262025-07-01911810.1186/s41927-025-00539-2Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization studyHui Yin0Tongxia Wang1Lin Liu2Zhi Hu3Department of Biochemistry and Molecular Biology, Basic Medical College, Qingdao UniversityShanghai Tenth People’s Hospital Chongming BranchDepartment of Thoracic Surgery, The First Affiliated Hospital of Shaoyang UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Shaoyang UniversityAbstract Background It is well-documented that systemic lupus erythematosus (SLE) is associated with asthma. However, the causal relationship between SLE and asthma, and the potential mediator need to be explained. This study aims to confirm the cause-and-effect relationship between SLE and asthma, and evaluate the mediation effect of lipid in European ancestry. Methods A Two-sample Mendelian randomization (MR) study was applied to analyze the causal relationships between SLE and asthma. A two-step MR design was used to explore whether low-density lipoprotein cholesterol (LDL-C) mediates the causal pathway from SLE to asthma outcome. Cochran’s Q statistic methods and MR-Egger regression were used to assess heterogeneity and pleiotropy. Leave-one-out (LOO) sensitivity test was adopted to estimate the effect of removing one of the selected individual SNPs on the overall results. Funnel and forest plots were also conducted to detect the pleiotropy directly. Results SLE was significantly associated with higher asthma risk according to inverse-variance weighted (IVW) method [OR (95%CI): 1.093 (1.024–1.166)] (P = 0.007), MR Egger method [OR (95%CI): 1.192 (1.077–1.319)] (P = 0.028) and Maximum likelihood [OR (95%CI): 1.094 (1.036–1.155)] (P = 0.001), which were robust across adequate sensitivity analysis. On the contrary, asthma has no causal relationship with SLE. In addition, LDL-C may mediate a proportion of 6.15% of the total effect between SLE and asthma. Conclusion This study demonstrates that patients with SLE may have a higher risk of developing asthma, which may be mediated by LDL-C. Understanding this relationship provides insight into potential mechanisms underlying asthma development in SLE patients and offers a foundation for developing targeted treatment strategies to manage these risks effectively.https://doi.org/10.1186/s41927-025-00539-2HumanSystemic lupus erythematosusAsthmaLow-density lipoprotein cholesterolGenetic association |
| spellingShingle | Hui Yin Tongxia Wang Lin Liu Zhi Hu Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization study BMC Rheumatology Human Systemic lupus erythematosus Asthma Low-density lipoprotein cholesterol Genetic association |
| title | Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization study |
| title_full | Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization study |
| title_fullStr | Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization study |
| title_full_unstemmed | Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization study |
| title_short | Low-density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma: a mediation mendelian randomization study |
| title_sort | low density lipoprotein cholesterol mediates the causal association between systemic lupus erythematosus and asthma a mediation mendelian randomization study |
| topic | Human Systemic lupus erythematosus Asthma Low-density lipoprotein cholesterol Genetic association |
| url | https://doi.org/10.1186/s41927-025-00539-2 |
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