Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study
Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1242614/full |
| _version_ | 1797754611413549056 |
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| author | Meiti Wang Guixiang Jin Ying Cheng Shi-Yang Guan Jinxin Zheng Shun-Xian Zhang |
| author_facet | Meiti Wang Guixiang Jin Ying Cheng Shi-Yang Guan Jinxin Zheng Shun-Xian Zhang |
| author_sort | Meiti Wang |
| collection | DOAJ |
| description | Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis.Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods.Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) −18, IL-1β, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines.Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved. |
| first_indexed | 2024-03-12T17:34:56Z |
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| id | doaj.art-c408fc4a622a4ac4b72f91d11679313d |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T17:34:56Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-c408fc4a622a4ac4b72f91d11679313d2023-08-04T12:09:08ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-08-011410.3389/fgene.2023.12426141242614Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization studyMeiti Wang0Guixiang Jin1Ying Cheng2Shi-Yang Guan3Jinxin Zheng4Shun-Xian Zhang5Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Yangpu Mental Health Center, Shanghai, ChinaShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSecond Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaSchool of Global Health, Chinese Center for Tropical Diseases Research—Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaClinical Research Center, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaObjective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis.Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods.Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) −18, IL-1β, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines.Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved.https://www.frontiersin.org/articles/10.3389/fgene.2023.1242614/fullmajor depressive disorderinflammatory cytokineMendelian randomizationGWASIL-18RANTES |
| spellingShingle | Meiti Wang Guixiang Jin Ying Cheng Shi-Yang Guan Jinxin Zheng Shun-Xian Zhang Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study Frontiers in Genetics major depressive disorder inflammatory cytokine Mendelian randomization GWAS IL-18 RANTES |
| title | Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study |
| title_full | Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study |
| title_fullStr | Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study |
| title_full_unstemmed | Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study |
| title_short | Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study |
| title_sort | genetically predicted circulating levels of cytokines and the risk of depression a bidirectional mendelian randomization study |
| topic | major depressive disorder inflammatory cytokine Mendelian randomization GWAS IL-18 RANTES |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1242614/full |
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