Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis
Background: The association between immune imbalances and adverse pregnancy outcomes has been extensive investigated by observational studies, but remain unclear. Thus, this study aimed to establish the causality of the circulation levels of cytokines on adverse pregnancy outcomes, such as offspring...
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Frontiers Media S.A.
2023-02-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1113804/full |
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| author | Honghong Wang Honghong Wang Honghong Wang Honghong Wang Jinghang Jiang Jinghang Jiang Jinghang Jiang Tingwei Jin Tingwei Jin Yifu Wang Yifu Wang Mingli Li Mingli Li Shengzhu Huang Shengzhu Huang Juanjuan Xie Juanjuan Xie Zhongyuan Chen Zhongyuan Chen Yi Guo Yi Guo Jie Zheng Jie Zheng Yonghua Jiang Yonghua Jiang Yonghua Jiang Zengnan Mo Zengnan Mo Zengnan Mo |
| author_facet | Honghong Wang Honghong Wang Honghong Wang Honghong Wang Jinghang Jiang Jinghang Jiang Jinghang Jiang Tingwei Jin Tingwei Jin Yifu Wang Yifu Wang Mingli Li Mingli Li Shengzhu Huang Shengzhu Huang Juanjuan Xie Juanjuan Xie Zhongyuan Chen Zhongyuan Chen Yi Guo Yi Guo Jie Zheng Jie Zheng Yonghua Jiang Yonghua Jiang Yonghua Jiang Zengnan Mo Zengnan Mo Zengnan Mo |
| author_sort | Honghong Wang |
| collection | DOAJ |
| description | Background: The association between immune imbalances and adverse pregnancy outcomes has been extensive investigated by observational studies, but remain unclear. Thus, this study aimed to establish the causality of the circulation levels of cytokines on adverse pregnancy outcomes, such as offspring’s birthweight (BW), preterm birth (PTB), spontaneous miscarriage (SM), and stillbirth (SB).Methods: Two-sample Mendelian randomization (MR) analysis was employed to investigate potential causal relations between 41 cytokines and pregnancy outcomes on the basis of previously published GWAS datasets. Multivariable MR (MVMR) analysis was implemented to investigate the effect of the composition of cytokine networks on the pregnancy outcomes. Potential risk factors were further estimated to explore the potential mediators.Results: Genetic correlation analysis based on large GWAS data sources revealed that genetically predicted MIP1b (β = −0.027, S.E. = 0.010, p = 0.009) and MCSF (β = −0.024, S.E. = 0.011, p = 0.029) were associated with reduced offspring’s BW, MCP1 (OR: 0.90, 95% CI: 0.83–0.97, p = 0.007) was associated with reduced SM risk, SCF (β = −0.014, S.E. = 0.005, p = 0.012) associated with decreased number of SB in MVMR. The univariable MR showed that GROa (OR: 0.92, 95% CI: 0.87–0.97, p = 0.004) was associated with decreased PTB risk. Except for the MCSF-BW association, all above associations surpassed the Bonferroni corrected threshold. The MVMR results revealed that MIF, SDF1a, MIP1b, MCSF and IP10 composed cytokine networks, associated with offspring’s BW. Risk factors analysis indicated that the above causal associations might be mediated by smoking behaviors.Conclusion: These findings suggest the causal associations of several cytokines with adverse pregnancy outcomes, which were potentially mediated by smoking and obesity. Some of the results did not been corrected through multiple tests and larger samples verification is required in further studies. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-dfa7a6e1a7784f11850018f32271de862023-02-20T04:56:32ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-02-011410.3389/fgene.2023.11138041113804Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysisHonghong Wang0Honghong Wang1Honghong Wang2Honghong Wang3Jinghang Jiang4Jinghang Jiang5Jinghang Jiang6Tingwei Jin7Tingwei Jin8Yifu Wang9Yifu Wang10Mingli Li11Mingli Li12Shengzhu Huang13Shengzhu Huang14Juanjuan Xie15Juanjuan Xie16Zhongyuan Chen17Zhongyuan Chen18Yi Guo19Yi Guo20Jie Zheng21Jie Zheng22Yonghua Jiang23Yonghua Jiang24Yonghua Jiang25Zengnan Mo26Zengnan Mo27Zengnan Mo28Center for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaSchool of Public Health, Guangxi Medical University, Nanning, Guangxi, ChinaDepartment of Pharmacy, Liuzhou Maternity and Child Healthcare Hospital, Affiliated Maternity Hospital and Affiliated Children’s Hospital of Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaDepartment of Pharmacy, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, Liuzhou, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaInstitute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaThe Reproductive Medicine Center, Jingmen No. 2 People’s Hospital, JingChu University of Technology Affiliated Central Hospital, Jingmen, Hubei, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaInstitute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaInstitute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaSchool of Public Health, Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaSchool of Public Health, Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaInstitute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Collaborative Innovation Center for Biomedicine (Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment), Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaInstitute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaInstitute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaDepartment of Gynecology, The Second Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaLife Sciences Institute, Guangxi Medical University, Nanning, Guangxi, ChinaCenter for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaSchool of Public Health, Guangxi Medical University, Nanning, Guangxi, ChinaInstitute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaBackground: The association between immune imbalances and adverse pregnancy outcomes has been extensive investigated by observational studies, but remain unclear. Thus, this study aimed to establish the causality of the circulation levels of cytokines on adverse pregnancy outcomes, such as offspring’s birthweight (BW), preterm birth (PTB), spontaneous miscarriage (SM), and stillbirth (SB).Methods: Two-sample Mendelian randomization (MR) analysis was employed to investigate potential causal relations between 41 cytokines and pregnancy outcomes on the basis of previously published GWAS datasets. Multivariable MR (MVMR) analysis was implemented to investigate the effect of the composition of cytokine networks on the pregnancy outcomes. Potential risk factors were further estimated to explore the potential mediators.Results: Genetic correlation analysis based on large GWAS data sources revealed that genetically predicted MIP1b (β = −0.027, S.E. = 0.010, p = 0.009) and MCSF (β = −0.024, S.E. = 0.011, p = 0.029) were associated with reduced offspring’s BW, MCP1 (OR: 0.90, 95% CI: 0.83–0.97, p = 0.007) was associated with reduced SM risk, SCF (β = −0.014, S.E. = 0.005, p = 0.012) associated with decreased number of SB in MVMR. The univariable MR showed that GROa (OR: 0.92, 95% CI: 0.87–0.97, p = 0.004) was associated with decreased PTB risk. Except for the MCSF-BW association, all above associations surpassed the Bonferroni corrected threshold. The MVMR results revealed that MIF, SDF1a, MIP1b, MCSF and IP10 composed cytokine networks, associated with offspring’s BW. Risk factors analysis indicated that the above causal associations might be mediated by smoking behaviors.Conclusion: These findings suggest the causal associations of several cytokines with adverse pregnancy outcomes, which were potentially mediated by smoking and obesity. Some of the results did not been corrected through multiple tests and larger samples verification is required in further studies.https://www.frontiersin.org/articles/10.3389/fgene.2023.1113804/fullMendelian randomizationcytokinesimmune systembirthweightspontaneous miscarriagesstillbirth |
| spellingShingle | Honghong Wang Honghong Wang Honghong Wang Honghong Wang Jinghang Jiang Jinghang Jiang Jinghang Jiang Tingwei Jin Tingwei Jin Yifu Wang Yifu Wang Mingli Li Mingli Li Shengzhu Huang Shengzhu Huang Juanjuan Xie Juanjuan Xie Zhongyuan Chen Zhongyuan Chen Yi Guo Yi Guo Jie Zheng Jie Zheng Yonghua Jiang Yonghua Jiang Yonghua Jiang Zengnan Mo Zengnan Mo Zengnan Mo Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis Frontiers in Genetics Mendelian randomization cytokines immune system birthweight spontaneous miscarriages stillbirth |
| title | Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis |
| title_full | Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis |
| title_fullStr | Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis |
| title_full_unstemmed | Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis |
| title_short | Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis |
| title_sort | associations of circulation levels of cytokines with birthweight preterm birth spontaneous miscarriages and stillbirth a mendelian randomization analysis |
| topic | Mendelian randomization cytokines immune system birthweight spontaneous miscarriages stillbirth |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1113804/full |
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