Systemic inflammatory regulators and primary ovarian insufficiency: a bidirectional Mendelian randomization study

Jiahui Wang, Xia Zhao, Rong Luo, Di Xia, Yi Liu, Tao Shen, Yuanjiao Liang
In: Research Square · 2023 · doi:10.21203/rs.3.rs-2816996/v1 · W4366389832
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Abstract

Abstract Background : 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. Results : 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 ) 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 vascular endothelial growth factor (odds ratio [OR] = 0.73, 95% confidence interval [CI]: 0.54–0.99, P=0.046) and interleukin-10 (OR=0.53, 95% CI: 0.33–0.85, P=0.0091) exhibit protective effects on POI. Reverse MR analysis revealed no significant effect of POI on these 41 systemic inflammatory regulators. No notable heterogeneity or horizontal pleiotropy was observed in the instrumental variables. Conclusions : This study revealed a causal relationship between 41 systemic inflammatory regulators and POI. Further investigations are necessary to assess the potential of these biomarkers as diagnostic tools, preventive strategies, and therapeutic targets for POI.

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