The causal association between systemic inflammatory regulators and primary ovarian insufficiency: a bidirectional mendelian randomization study

孟德尔随机化 多效性 医学 优势比 内科学 置信区间 肿瘤科 生物信息学 生物 遗传学 表型 基因 基因型 遗传变异
作者
Jiahui Wang,Xia Zhao,Rong Luo,Di Xia,Yi Liu,Tao Shen,Yuanjiao Liang
出处
期刊:Journal of Ovarian Research [BioMed Central]
卷期号:16 (1) 被引量:8
标识
DOI:10.1186/s13048-023-01272-5
摘要

Recent studies have suggested a potential link between systemic inflammatory regulators and primary ovarian insufficiency (POI); however, a causal relationship between them remains unclear. In this study, we explored the causal link between systemic inflammatory regulators and POI risk using a bidirectional, two-sample Mendelian randomization (MR) strategy.This approach utilized the most extensive genome-wide association study involving 41 systemic inflammatory regulators in a sample of 8,293 Finnish individuals and POI data from the FinnGen consortium (254 cases vs. 118,228 controls). The inverse variance weighting approach served as a primary MR method, and four additional MR techniques (Maximum Likelihood, MR-Egger, Weighted Median, and constrained maximum likelihood and model averaging Bayesian information criterion ) were applied to support and validate results. Cochran's Q statistics were used to assess the heterogeneity of instrumental variables, whereas the MR-Egger and MR Pleiotropy Residual Sum and Outlier tests detected horizontal pleiotropy. The MR Steiger test evaluated the strength of a causal association. Our findings suggest that lower levels of vascular endothelial growth factor (odds ratio [OR] = 0.73, 95% confidence interval [CI]: 0.54-0.99, P = 0.046) and interleukin-10 (OR = 0.54, 95% CI: 0.33-0.85, P = 0.021) are associated with an increased risk of POI. Reverse MR analysis revealed no significant effect of POI on the expression of these 41 systemic inflammatory regulators. No notable heterogeneity or horizontal pleiotropy was observed in the instrumental variables.This study revealed a causal association between 41 systemic inflammatory regulators and POI, demonstrating that decreased levels of VEGF and IL-10 are linked to an elevated risk of POI. Further investigations are necessary to assess the potential of these biomarkers as early predictors, preventive strategies, and therapeutic targets for POI.
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