Causal Relationship between Serum Metabolites, Plasma Lipids, and Hemorrhoidal Disease: A Mendelian Randomization Study

Abstract Hemorrhoidal Disease (HD) is a common anorectal disorder that significantly impacts patients' quality of life over the long term and imposes a substantial economic burden. However, the potential link between HD and serum metabolites and lipids has been scarcely studied, and its pathogenesis remains unclear. In this study, the causal relationship between serum metabolite traits, plasma lipids, and HD was evaluated using Mendelian Randomization (MR). Three methods were employed to estimate the causal effect of exposure on outcomes. The study identified 27 serum metabolic traits and 4 plasma lipids with significant causal effects on HD. Among these, 11 serum metabolic traits were identified as risk factors, and the top three ones exhibiting the most significant causal effects on the outcomes are Cortolone glucuronide (1) levels(OR=1.544, 95%CI=1.124-2.123,p=0.007), 3-methyl-2-oxobutyrate levels(OR=2.079, 95%CI=1.189-3.635,p=0.010), and Glycocholate levels(OR=1.405, 95%CI=1.063-1.857, p=0.017). Additionally, 16 serum metabolic traits were found to be protective factors, with lipids or lipoids and their metabolites comprising the largest proportion. In the Mendelian randomization analysis of plasma lipids and HD,Phosphatidylcholine (18:2_20:4) (OR=1.588,95%CI=1.097-2.299,p=0.014) and Phosphatidylcholine (O-16:1_16:0) (OR=1.676，95%CI=1.109-2.533,p=0.014) were identified as risk factors for HD.