Associations between genetically predicted concentrations of circulating inflammatory cytokines and the risk of ten pregnancy-related adverse outcomes: A two-sample Mendelian randomization study

作者全名：Chen, Xinzhen; Zhang, Min; Zhou, Niya; Zhou, Wei; Qi, Hongbo

作者地址：[Chen, Xinzhen; Zhang, Min; Zhou, Niya] Chongqing Med Univ, Women & Childrens Hosp, Clin Res Ctr, Chongqing 401147, Peoples R China; [Chen, Xinzhen; Zhang, Min; Zhou, Niya] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Res Ctr Prevent & Control Maternal & Chi, Chongqing 401147, Peoples R China; [Zhou, Wei; Qi, Hongbo] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynaecol, 120 Longshan Rd, Chongqing 401147, Peoples R China

通信作者：Qi, HB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynaecol, 120 Longshan Rd, Chongqing 401147, Peoples R China.

来源：CYTOKINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001247479300001

JCR分区：Q2

影响因子：3.7

年份：2024

卷号：180

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Mendelian randomization; Circulating cytokine; Systemic inflammation; Pregnancy-related adverse outcomes; FinnGen

摘要：Background: Evidence from increasing observational studies indicates that systemic inflammation plays a role in pregnancy-related adverse events. However, the causal associations between them are largely unclear. To investigate the potential causal effects of genetically regulated concentrations of inflammatory cytokines on the risk of adverse pregnancy outcomes, we performed a Mendelian randomization (MR) analysis. Methods: The cis-protein quantitative trait loci for the 47 inflammatory cytokines derived from the latest genome-wide association studies (GWASs) consisting of 31,112 European individuals were used as the instrumental variables. The latest GWAS summary data for the ten adverse pregnancy events were obtained from the FinnGen project (samples ranging from 141,014 to 190,879). The inverse-variance weighted regression or Ward ratio was used as the primary MR analysis method. Sensitivity analyses based on the other five methods were performed to verify MR results. A replication MR analysis was conducted to further clarify the significant associations using data from the UK Biobank. Results: Twenty-three of the 220 associations were nominally significant (P < 0.05). Among them, seven robust associations survived the Bonferroni correction and passed sensitivity analyses, including positive associations of soluble intercellular adhesion molecule (sICAM-1) with the risk of excessive vomiting in pregnancy, preeclampsia (PE), and pregnancy hypertension (PH), vascular endothelial growth factor with the risk of medical abortion, macrophage colony-stimulating factor (MCSF) with the risk of spontaneous abortion (SA), and an inverse association of macrophage inflammatory protein-1 alpha with the risk of medical abortion. The associations of MCSF with SA, and sICAM-1 with both PE and PH were further confirmed in the replication analysis. Conclusions: This study provides further evidence of the role of systemic inflammation, especially endothelial dysfunction in the pathology of adverse pregnancy events, and the identified cytokines warrant in-depth research to explore their underlying mechanisms of action and to evaluate their potential as targets for disease screening, prevention, and treatment in the future.

基金机构：Key Projects of the National Natural Science Foundation of China [8213 0097]; Chongqing Science and Health Joint Tackling Project [2023GGXM005]; Chongqing Research Centre for Prevention & Control of Maternal and Child Diseases and Public Health

基金资助正文：This work was supported by the Key projects of the National Natural Science Foundation of China (grant number 8213 0097) , the Chongqing Science and Health Joint Tackling Project (grant number 2023GGXM005) , and the Chongqing Research Centre for Prevention & Control of Maternal and Child Diseases and Public Health. The sponsors had no involvement in the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the article for publication.