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

objectiveEndometriosis (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.

methodsUsing 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.

resultsMR 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.

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