Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization
BackgroundIntervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relations...
| Auteurs principaux: | , , , , , , , |
|---|---|
| Format: | Article |
| Langue: | English |
| Publié: |
Frontiers Media S.A.
2024-01-01
|
| Collection: | Frontiers in Immunology |
| Sujets: | |
| Accès en ligne: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1321295/full |
| _version_ | 1827385787460616192 |
|---|---|
| author | Chaofan Qin Mingxin Chen Qingshuai Yu Xin Wang Tao Hu Bo Lei Zhengjian Yan Si Cheng |
| author_facet | Chaofan Qin Mingxin Chen Qingshuai Yu Xin Wang Tao Hu Bo Lei Zhengjian Yan Si Cheng |
| author_sort | Chaofan Qin |
| collection | DOAJ |
| description | BackgroundIntervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relationship between immunity and disc degeneration remains to be fully elucidated.MethodWe obtained GWAS data for immune cells from the latest summary-level GWAS, including 6,620 individuals from Sardinian and 746,667 individuals from five global populations. Summary results for IVDD were sourced from the FinnGen consortium, comprising 20,001 cases and 164,682 controls. We conducted a comprehensive univariable Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and IVDD. Primary estimation was carried out using Inverse-Variance Weighting (IVW). To ensure robustness, we employed additional MR methods such as MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Various tests were employed to assess pleiotropy and heterogeneity, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis and MR-PRESSO test. To account for potential confounding factors among the immune cells, we conducted a multivariable MR analysis. Finally, we investigated the possibility of a reverse association between immune cells and IVDD through bidirectional MR.ResultIn total, our study identified 15 immune cells significantly associated with IVDD through univariable MR. Among these, 9 immune cell types were indicated as potential contributors to IVDD, while 6 were found to have protective effects. Importantly, we observed no evidence of heterogeneity or pleiotropy, signifying the robustness of our results. To mitigate confounding among immune cells, we utilized multivariable MR, leading to the discovery that only 9 immune cell types exerted independent effects on IVDD. These encompassed 7 as risk factors and 2 as protective factors. Additionally, our analysis revealed a bidirectional causal relationship between CD39+ CD4+ T cell %CD4+ T cell and IVDD.ConclusionOur findings suggest a connection between immune cells and the risk of IVDD, shedding light on potential therapeutic avenues for modulating immune cell function in individuals with IVDD. However, the specific underlying mechanisms warrant further investigation in future experiments. |
| first_indexed | 2024-03-08T15:31:39Z |
| format | Article |
| id | doaj.art-71f337ce676b4173bbb5a36f67df3db6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T15:31:39Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-71f337ce676b4173bbb5a36f67df3db62024-01-10T04:31:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.13212951321295Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomizationChaofan QinMingxin ChenQingshuai YuXin WangTao HuBo LeiZhengjian YanSi ChengBackgroundIntervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relationship between immunity and disc degeneration remains to be fully elucidated.MethodWe obtained GWAS data for immune cells from the latest summary-level GWAS, including 6,620 individuals from Sardinian and 746,667 individuals from five global populations. Summary results for IVDD were sourced from the FinnGen consortium, comprising 20,001 cases and 164,682 controls. We conducted a comprehensive univariable Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and IVDD. Primary estimation was carried out using Inverse-Variance Weighting (IVW). To ensure robustness, we employed additional MR methods such as MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Various tests were employed to assess pleiotropy and heterogeneity, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis and MR-PRESSO test. To account for potential confounding factors among the immune cells, we conducted a multivariable MR analysis. Finally, we investigated the possibility of a reverse association between immune cells and IVDD through bidirectional MR.ResultIn total, our study identified 15 immune cells significantly associated with IVDD through univariable MR. Among these, 9 immune cell types were indicated as potential contributors to IVDD, while 6 were found to have protective effects. Importantly, we observed no evidence of heterogeneity or pleiotropy, signifying the robustness of our results. To mitigate confounding among immune cells, we utilized multivariable MR, leading to the discovery that only 9 immune cell types exerted independent effects on IVDD. These encompassed 7 as risk factors and 2 as protective factors. Additionally, our analysis revealed a bidirectional causal relationship between CD39+ CD4+ T cell %CD4+ T cell and IVDD.ConclusionOur findings suggest a connection between immune cells and the risk of IVDD, shedding light on potential therapeutic avenues for modulating immune cell function in individuals with IVDD. However, the specific underlying mechanisms warrant further investigation in future experiments.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1321295/fullimmune cellsintervertebral disc degenerationmultivariable mendelian randomizationunivariable mendelian randomizationbidirectional mendelian randomization |
| spellingShingle | Chaofan Qin Mingxin Chen Qingshuai Yu Xin Wang Tao Hu Bo Lei Zhengjian Yan Si Cheng Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization Frontiers in Immunology immune cells intervertebral disc degeneration multivariable mendelian randomization univariable mendelian randomization bidirectional mendelian randomization |
| title | Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization |
| title_full | Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization |
| title_fullStr | Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization |
| title_full_unstemmed | Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization |
| title_short | Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization |
| title_sort | causal relationship between the blood immune cells and intervertebral disc degeneration univariable bidirectional and multivariable mendelian randomization |
| topic | immune cells intervertebral disc degeneration multivariable mendelian randomization univariable mendelian randomization bidirectional mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1321295/full |
| work_keys_str_mv | AT chaofanqin causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization AT mingxinchen causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization AT qingshuaiyu causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization AT xinwang causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization AT taohu causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization AT bolei causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization AT zhengjianyan causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization AT sicheng causalrelationshipbetweenthebloodimmunecellsandintervertebraldiscdegenerationunivariablebidirectionalandmultivariablemendelianrandomization |