SPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysis
Abstract Background The incidence of rheumatoid arthritis (RA) is rising. However, its pathogenesis has not been fully understood, and the current therapeutic regimens are still limited. The aim of this study was to investigate the causal effect of plasma proteins on RA using Mendelian randomization...
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BMC
2025-06-01
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| Series: | BMC Rheumatology |
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| Online Access: | https://doi.org/10.1186/s41927-025-00521-y |
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| author | Kun Lin Qi Lin Weifeng Lv Yao Li Rong Su |
| author_facet | Kun Lin Qi Lin Weifeng Lv Yao Li Rong Su |
| author_sort | Kun Lin |
| collection | DOAJ |
| description | Abstract Background The incidence of rheumatoid arthritis (RA) is rising. However, its pathogenesis has not been fully understood, and the current therapeutic regimens are still limited. The aim of this study was to investigate the causal effect of plasma proteins on RA using Mendelian randomization (MR) analysis. Methods We performed MR analysis with 4907 plasma protein genetic associations used for exposure and RA genome-wide association data used as outcomes. The method was dominated by Inverse Variance Weighting, in addition to MR-Egger and Weighted Median. Meanwhile, further external validation and reverse MR analysis were conducted to systematically assess the causal relationship between plasma proteins and RA. Result Preliminary MR analysis identified two proteins (SPAG11B and DEFB135) associated with RA, and elevated plasma levels of both proteins would reduce the risk of RA (for SPAG11B, OR = 0.49, 95% CI = 0.40–0.61, p = 1.19 × 10− 10; for DEFB135, OR = 0.28, 95% CI = 0.15–0.52, p = 4.51 × 10− 5, using the IVW method). In the external validation phase, the results were reproducible for SPAG11B, but not for DEFB135. Reverse MR analysis pointed out that RA exhibited reverse causality for plasma levels of SPAG11B (OR = 0.93, 95% CI = 0.89–0.98, p = 0.004), but not for DEFB135 (p = 0.93). Conclusion The results of MR analysis in this study supported that SPAG11B as a novel biomarker for RA was worthy of further investigation. |
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| institution | OA Journals |
| issn | 2520-1026 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | BMC Rheumatology |
| spelling | doaj-art-94d2b604f78a42de87bd7a8617ebd2972025-08-20T02:05:42ZengBMCBMC Rheumatology2520-10262025-06-019111010.1186/s41927-025-00521-ySPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysisKun Lin0Qi Lin1Weifeng Lv2Yao Li3Rong Su4The Eighth Clinical Medical College of Guangzhou University of Chinese MedicineThe Eighth Clinical Medical College of Guangzhou University of Chinese MedicineThe Eighth Clinical Medical College of Guangzhou University of Chinese MedicineThe Eighth Clinical Medical College of Guangzhou University of Chinese MedicineThe Eighth Clinical Medical College of Guangzhou University of Chinese MedicineAbstract Background The incidence of rheumatoid arthritis (RA) is rising. However, its pathogenesis has not been fully understood, and the current therapeutic regimens are still limited. The aim of this study was to investigate the causal effect of plasma proteins on RA using Mendelian randomization (MR) analysis. Methods We performed MR analysis with 4907 plasma protein genetic associations used for exposure and RA genome-wide association data used as outcomes. The method was dominated by Inverse Variance Weighting, in addition to MR-Egger and Weighted Median. Meanwhile, further external validation and reverse MR analysis were conducted to systematically assess the causal relationship between plasma proteins and RA. Result Preliminary MR analysis identified two proteins (SPAG11B and DEFB135) associated with RA, and elevated plasma levels of both proteins would reduce the risk of RA (for SPAG11B, OR = 0.49, 95% CI = 0.40–0.61, p = 1.19 × 10− 10; for DEFB135, OR = 0.28, 95% CI = 0.15–0.52, p = 4.51 × 10− 5, using the IVW method). In the external validation phase, the results were reproducible for SPAG11B, but not for DEFB135. Reverse MR analysis pointed out that RA exhibited reverse causality for plasma levels of SPAG11B (OR = 0.93, 95% CI = 0.89–0.98, p = 0.004), but not for DEFB135 (p = 0.93). Conclusion The results of MR analysis in this study supported that SPAG11B as a novel biomarker for RA was worthy of further investigation.https://doi.org/10.1186/s41927-025-00521-yRheumatoid arthritisPlasma proteinSPAG11BDEFB135Mendelian randomization |
| spellingShingle | Kun Lin Qi Lin Weifeng Lv Yao Li Rong Su SPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysis BMC Rheumatology Rheumatoid arthritis Plasma protein SPAG11B DEFB135 Mendelian randomization |
| title | SPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysis |
| title_full | SPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysis |
| title_fullStr | SPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysis |
| title_full_unstemmed | SPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysis |
| title_short | SPAG11B, a potential biomarker for rheumatoid arthritis: a two-sample bidirectional Mendelian randomization analysis |
| title_sort | spag11b a potential biomarker for rheumatoid arthritis a two sample bidirectional mendelian randomization analysis |
| topic | Rheumatoid arthritis Plasma protein SPAG11B DEFB135 Mendelian randomization |
| url | https://doi.org/10.1186/s41927-025-00521-y |
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