Abstract
Background and Aims: Endometriosis is a chronic gynecological disease with a high prevalence among reproductive-aged women. Several studies have investigated the causal effect of different serum biomarkers of immunity and inflammation on the occurrence and progression of endometriosis. However, the results of these studies remained inconclusive and even controversial. Herein, this study aims to analyze the causal associations of genetically predicted levels of different circulating biomarkers of immunity and inflammation with the risk of endometriosis using a bidirectional two-sample Mendelian randomization (MR) approach. Methods: The single-nucleotide polymorphisms (SNPs) of exposures which indicate the genetic variants were used as instrumental variables (IVs) and were all obtained from the genome-wide association study (GWAS) of European ancestry from the IEU GWAS database. Besides, we performed bidirectional MR analysis to test the associations. The causal effects were estimated through the inverse-variance weighted method (IVW). The sensitivity examinations of each result after the MR analysis were performed to detect if any heterogeneity and pleiotropy existed. Results: Our results demonstrated that higher interleukin-9 (IL-9) level was associated with the occurrence of endometriosis, while macrophage colony stimulating factor (MCSF) level, TNF-related apoptosis inducing ligand (TRAIL), sE-Selectin and basophil count showed the opposite. Genetically predicted endometriosis was related to higher immunoglobulin E (IgE) level and platelet count. No evidence of bidirectional association was detected on the other serum inflammatory biomarkers with endometriosis. Neither pleiotropy nor heterogeneity was found in our study. Conclusion: Our results suggested that some dysregulated circulating biomarkers of immunity and inflammation is causally associated with the occurrence of endometriosis, and at the same time endometriosis may lead to the abnormality of some of these factors. Our findings provided genetic insights on potential novel strategies in the primary prevention, diagnosis and treatment of endometriosis.
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