Association between circulating metabolites and endometriosis: a bidirectional two-sample Mendelian randomization study.

Abstract

Objective: Endometriosis (EM) is a chronic gynecological condition of unclear etiology, with evidence suggesting a link between metabolite levels and EM risk. A two-sample Mendelian randomization (MR) approach was used to explore the association between 233 metabolites and EM.

Methods: Using publicly available genetic data, we conducted a bidirectional two-sample MR analysis to assess the associations between metabolites and EM. Sensitivity analyses were performed to test robustness and pleiotropy, with Bonferroni correction applied for significance.

Results: MR analysis suggested that genetically elevated diacylglycerol levels were significantly associated with increased EM risk (odds ratio [OR], 1.225; P=1.16×10-7), corresponding to a 22.5% increase in risk per standard deviation increase in genetically predicted diacylglycerol levels, and remained significant after Bonferroni correction. Nominally significant associations were observed for several other metabolites; lower ratios of 3-hydroxybutyrate and saturated fatty acids to total fatty acids and of total cholesterol to total lipids in very low-density lipoproteins were associated with a higher EM risk (OR, 0.863; P=0.015; OR, 0.865; P=0.030; OR, 0.855; P=1.51×10-4). Reverse MR analysis showed that increased levels of conjugated linoleic acid (CLA) and tyrosine and the CLA to total fatty acid ratio exhibited nominal associations with EM (OR, 1.026; P=0.043; OR, 1.036; P=3.33×10-4; OR, 1.026; P=0.045). No significant heterogeneity or pleiotropy was observed.

Conclusion: This study provides evidence of an association between specific metabolites, especially diacylglycerol, and EM risk, enhancing our understanding of the metabolic profile associated with EM.