#213 : Causal Associations Between Different Plasma Lipid and Apolipoprotein Parameters with the Risk of Endometriosis: A Two-Sample Mendelian Randomization Study

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 plasma lipid and apolipoprotein parameters on the occurrence and progression of endometriosis. However, the results of these studies remained controversial. Herein, this study aims to analyze the causal associations of genetically predicted levels of different blood lipid and apolipoprotein traits with the risk of endometriosis using a 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). We assessed the correlation between each blood lipid and apolipoprotein parameter and the occurrence of endometriosis from various cohorts of European ancestry, and the SNPs of them were obtained from the genome-wide association study (GWAS) from the IEU GWAS database. 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. Besides, sub-analyses were performed to provide more detailed information about the actual associations.

Results: Our results demonstrated that cholesterol in chylomicron (CM) and extremely large very low-density lipoprotein (VLDL) was causally linked to higher odds of endometriosis, while high-density lipoprotein (HDL) cholesterol showed the opposite correlation. No evidence was detected on the causal relations of low-density lipoprotein (LDL) cholesterol, VLDL cholesterol, triglyceride (TG), apolipoprotein A1 and apolipoprotein B with endometriosis. Neither pleiotropy nor heterogeneity was found in our study. In addition, subgroup analyses about subtypes of endometriosis suggested the causal association of several serum lipids with peritoneal endometriosis.

Conclusion: Our results suggested that dysregulated lipid metabolism is causally associated with the occurrence of endometriosis, especially peritoneal endometriosis. Our findings provided genetic insights on potential novel strategies in the primary prevention and treatment of endometriosis.