Relationship Between the Levels of 91 Circulating Inflammatory Proteins and Ovarian-Related Diseases: A Bidirectional Mendelian Randomization Study

Jiahui Qu, Liying Zhang Department of Obstetrics and Gynecology, the Second Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Liying Zhang, Department of Obstetrics and Gynecology, the Second Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China, Email [email protected]: Inflammatory proteins play a pivotal role in the pathogenesis of ovarian diseases, although the underlying mechanisms remain poorly understood. The aim of this study is to investigate the association between circulating markers of inflammation and ovarian diseases.Methods: A two-sample bidirectional Mendelian randomization (MR) approach was employed, utilizing publicly available genetic databases to examine the relationship between 91 circulating inflammatory markers and six ovarian diseases. The primary analysis utilized the inverse variance weighting (IVW) method, with additional sensitivity analyses, including heterogeneity and pleiotropy tests, to assess the robustness of the findings.Results: Specific inflammatory markers were found to be associated with ovarian diseases and to exhibit causal relationships. Ovarian cysts were linked to CCL4 and other proteins, showing a positive causal relationship with NT-3. Polycystic ovary syndrome (PCOS) was associated with IL-6 and other markers, with a positive causal relationship to IL-17C. Ovarian dysfunction was associated with IL-6 and other markers, while primary ovarian failure was linked to IL-33. Benign ovarian neoplasms were associated with CCL28 and other proteins, showing a positive causal relationship with FGF-19 and negative causal relationships with FGF-5 and NT-3. Malignant ovarian neoplasms were associated with CCL20 and other markers.Discussion: This study clarifies the causal relationships between circulating inflammatory markers and ovarian diseases, providing a crucial foundation for future translational research and clinical applications.Keywords: Mendelian randomization, circulating inflammatory protein, ovarian-related diseases, polycystic ovary syndrome, ovarian neoplasm