Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study
Abstract Background Several observational studies have suggested an association between low serum bilirubin levels and Behçet's disease uveitis. However, the causal inference between bilirubin level and juvenile idiopathic arthritis‐associated uveitis (JIAU) remains ambiguous. We investigated t...
| Main Authors: | , , , , |
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| Format: | Article |
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Wiley
2024-02-01
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| Series: | Health Science Reports |
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| Online Access: | https://doi.org/10.1002/hsr2.1847 |
| _version_ | 1797221175487627264 |
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| author | Jun Zhang Peng Zhou Shuqiong Hu Shiya Cai Tao He |
| author_facet | Jun Zhang Peng Zhou Shuqiong Hu Shiya Cai Tao He |
| author_sort | Jun Zhang |
| collection | DOAJ |
| description | Abstract Background Several observational studies have suggested an association between low serum bilirubin levels and Behçet's disease uveitis. However, the causal inference between bilirubin level and juvenile idiopathic arthritis‐associated uveitis (JIAU) remains ambiguous. We investigated the potential causal relationship between serum bilirubin levels and JIAU using a bidirectional two‐sample Mendelian randomization (MR) framework. Methods We systemically integrated summary‐level data from published large‐scale genome‐wide association studies on bilirubin level and JIAU in a Caucasian British population. To determine the causal effect of bilirubin level on JIAU, we constructed strong instrumental variables using 47 and 80 single‐nucleotide polymorphisms (SNPs) specific to direct bilirubin and total bilirubin levels, respectively. For reverse causal inference, seven SNPs associated with JIAU were included in our study. Multiple complementary methods were further performed to evaluate the robustness of MR estimates. Results The inverse‐variance weighted estimate did not show any significant causal associations of genetically predicted serum direct or total bilirubin level with the risk of JIAU (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 0.750–1.359, p = 0.947; OR: 0.867, 95% CI: 0.688–1.093; p = 0.227, respectively). MR–Egger and weighted median methods also obtained similar associations. Additionally, the results of reverse MR analyses using JIAU as exposure showed no associations of genetically predicted risk of JIAU with serum bilirubin levels (p > 0.05). In sensitivity analysis, the causal estimate between serum bilirubin levels and JIAU did not differ when SNPs associated with possible confounders were omitted. Conclusion Genetic evidence from our bidirectional analysis did not support a causal association between serum bilirubin levels and JIAU risk in the Caucasian British population. Future large‐scale studies should be conducted to validate these findings and explore any causal effects on the disease process. |
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| language | English |
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| spelling | doaj.art-d57e1b49fe7046b1b18e442836058e2e2024-04-05T11:41:32ZengWileyHealth Science Reports2398-88352024-02-0172n/an/a10.1002/hsr2.1847Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization studyJun Zhang0Peng Zhou1Shuqiong Hu2Shiya Cai3Tao He4Department of Ophthalmology Renmin Hospital of Wuhan University Wuhan Hubei ChinaCollege of Architecture Changsha University of Science and Technology Changsha Hunan ChinaWuhan Aier Eye Hospital of Wuhan University Wuhan Hubei ChinaDepartment of Ophthalmology, The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang ChinaDepartment of Ophthalmology Renmin Hospital of Wuhan University Wuhan Hubei ChinaAbstract Background Several observational studies have suggested an association between low serum bilirubin levels and Behçet's disease uveitis. However, the causal inference between bilirubin level and juvenile idiopathic arthritis‐associated uveitis (JIAU) remains ambiguous. We investigated the potential causal relationship between serum bilirubin levels and JIAU using a bidirectional two‐sample Mendelian randomization (MR) framework. Methods We systemically integrated summary‐level data from published large‐scale genome‐wide association studies on bilirubin level and JIAU in a Caucasian British population. To determine the causal effect of bilirubin level on JIAU, we constructed strong instrumental variables using 47 and 80 single‐nucleotide polymorphisms (SNPs) specific to direct bilirubin and total bilirubin levels, respectively. For reverse causal inference, seven SNPs associated with JIAU were included in our study. Multiple complementary methods were further performed to evaluate the robustness of MR estimates. Results The inverse‐variance weighted estimate did not show any significant causal associations of genetically predicted serum direct or total bilirubin level with the risk of JIAU (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 0.750–1.359, p = 0.947; OR: 0.867, 95% CI: 0.688–1.093; p = 0.227, respectively). MR–Egger and weighted median methods also obtained similar associations. Additionally, the results of reverse MR analyses using JIAU as exposure showed no associations of genetically predicted risk of JIAU with serum bilirubin levels (p > 0.05). In sensitivity analysis, the causal estimate between serum bilirubin levels and JIAU did not differ when SNPs associated with possible confounders were omitted. Conclusion Genetic evidence from our bidirectional analysis did not support a causal association between serum bilirubin levels and JIAU risk in the Caucasian British population. Future large‐scale studies should be conducted to validate these findings and explore any causal effects on the disease process.https://doi.org/10.1002/hsr2.1847bilirubincausal inferenceJIA associated uveitisMendelian randomizationsingle‐nucleotide polymorphism |
| spellingShingle | Jun Zhang Peng Zhou Shuqiong Hu Shiya Cai Tao He Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study Health Science Reports bilirubin causal inference JIA associated uveitis Mendelian randomization single‐nucleotide polymorphism |
| title | Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study |
| title_full | Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study |
| title_fullStr | Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study |
| title_full_unstemmed | Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study |
| title_short | Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study |
| title_sort | causal inference between serum bilirubin levels and juvenile idiopathic arthritis associated uveitis a bidirectional mendelian randomization study |
| topic | bilirubin causal inference JIA associated uveitis Mendelian randomization single‐nucleotide polymorphism |
| url | https://doi.org/10.1002/hsr2.1847 |
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