The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study
ObjectiveOsteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link betw...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1334361/full |
| _version_ | 1797357720211292160 |
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| author | Zong Jiang Xin Cai Xiaoling Yao Shaoqin Zhang Weiya Lan Zexu Jin Fang Tang Wukai Ma Xueming Yao Changming Chen Tianzuo Lan |
| author_facet | Zong Jiang Xin Cai Xiaoling Yao Shaoqin Zhang Weiya Lan Zexu Jin Fang Tang Wukai Ma Xueming Yao Changming Chen Tianzuo Lan |
| author_sort | Zong Jiang |
| collection | DOAJ |
| description | ObjectiveOsteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link between them remains ambiguous. This study aims to identify cytokines potentially causally related to OA using Mendelian randomization (MR) analysis, informing early clinical diagnosis and treatment decisions.MethodsWe conducted a genome-wide association study (GWAS) on 12 OA traits involving 177,517 cases and 649,173 controls from 9 international cohorts. For discovery MR analysis, we used 103 cytokines from two European populations as instrumental variables (IVs). Concurrently, another European population OA GWAS database (36,185 cases and 135,185 controls) was used to replicate MR analysis, employing the inverse variance weighted (IVW) method as the primary analytic approach. Additional methods tested included MR Egger, Weighted median, and Weighted mode. We merged the MR findings through meta-analysis. Heterogeneity testing, level pleiotropy testing (MR Egger intercept test and MRPRESSO), and sensitivity analysis via Leave One Out (LOO) were conducted to verify result robustness. Lastly, reverse MR analysis was performed.ResultsThe meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; P<0.010). We also observed associations between MCP4 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) and CCL25 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) with reduced OA risk. The sensitivity analysis results corroborate the robustness of these findings.ConclusionOur MR analysis indicates a potential causal relationship between CX3CL1, MCP4, CCL25, and OA risk changes. Further research is warranted to explore the influence of cytokines on OA development. |
| first_indexed | 2024-03-08T14:49:12Z |
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| id | doaj.art-ad9e185f85e74d96a704b63d66afb436 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T14:49:12Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-ad9e185f85e74d96a704b63d66afb4362024-01-11T04:55:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.13343611334361The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized studyZong Jiang0Xin Cai1Xiaoling Yao2Shaoqin Zhang3Weiya Lan4Zexu Jin5Fang Tang6Wukai Ma7Xueming Yao8Changming Chen9Tianzuo Lan10Second Clinical Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Rheumatology and Immunology, The First People's Hospital Of Guiyang, Guiyang, ChinaSecond Clinical Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Rheumatology and Immunology, The First People's Hospital Of Guiyang, Guiyang, ChinaSecond Clinical Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Rheumatology and Immunology, The First People's Hospital Of Guiyang, Guiyang, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Rheumatology and Immunology, The First People's Hospital Of Guiyang, Guiyang, ChinaObjectiveOsteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link between them remains ambiguous. This study aims to identify cytokines potentially causally related to OA using Mendelian randomization (MR) analysis, informing early clinical diagnosis and treatment decisions.MethodsWe conducted a genome-wide association study (GWAS) on 12 OA traits involving 177,517 cases and 649,173 controls from 9 international cohorts. For discovery MR analysis, we used 103 cytokines from two European populations as instrumental variables (IVs). Concurrently, another European population OA GWAS database (36,185 cases and 135,185 controls) was used to replicate MR analysis, employing the inverse variance weighted (IVW) method as the primary analytic approach. Additional methods tested included MR Egger, Weighted median, and Weighted mode. We merged the MR findings through meta-analysis. Heterogeneity testing, level pleiotropy testing (MR Egger intercept test and MRPRESSO), and sensitivity analysis via Leave One Out (LOO) were conducted to verify result robustness. Lastly, reverse MR analysis was performed.ResultsThe meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; P<0.010). We also observed associations between MCP4 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) and CCL25 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) with reduced OA risk. The sensitivity analysis results corroborate the robustness of these findings.ConclusionOur MR analysis indicates a potential causal relationship between CX3CL1, MCP4, CCL25, and OA risk changes. Further research is warranted to explore the influence of cytokines on OA development.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1334361/fullcytokinesosteoarthritisMendelian randomizationbidirectionalmeta analysis |
| spellingShingle | Zong Jiang Xin Cai Xiaoling Yao Shaoqin Zhang Weiya Lan Zexu Jin Fang Tang Wukai Ma Xueming Yao Changming Chen Tianzuo Lan The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study Frontiers in Immunology cytokines osteoarthritis Mendelian randomization bidirectional meta analysis |
| title | The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study |
| title_full | The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study |
| title_fullStr | The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study |
| title_full_unstemmed | The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study |
| title_short | The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study |
| title_sort | causal effect of cytokine cycling levels on osteoarthritis a bidirectional mendelian randomized study |
| topic | cytokines osteoarthritis Mendelian randomization bidirectional meta analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1334361/full |
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