Investigating Causal Links between Metabolite Profiles and Ulcerative Colitis: A Bidirectional Mendelian Randomization Study

Abstract

Background:While metabolic biomarkers are known to play a significant role in the development of ulcerative colitis (UC), the exact causal relationships between them remain uncertain and warrant further investigations. Here we report a bidirectional two-sample Mendelian randomization (MR) study to evaluate causal relationships between 503 blood metabolites and UC.Methods:We used genome-wide association study (GWAS) data on blood metabolite levels from two separate studies on European individuals (n = 8299 and 24,925). In addition, for UC, we utilized GWAS data from the same ancestry, including 417,932 participants, comprising 5371 UC cases and 412,561 controls. We employed the inverse variance weighted method for our discovery stage of MR analyses. Then, we used other methods, including MR-Egger, weighted median, weighted mode, simple mode, MR-pleiotropy residual sum and outlier, heterogeneity, and pleiotropy tests for sensitivity analyses to further validate our findings and assess the robustness of our results.Results:Our study suggests that total lipids in small high-density lipoprotein levels (S.HDL.L) are marginal significant positive associated with the development of UC (odds ratio = 1.167, 95 confidence interval: 0.998-1.364, P = 0.051). In addition, UC did not have a statistically significant effect on the metabolites.Conclusions:Total lipids in S.HDL.L may offer a potential trend as valuable circulating metabolic biomarkers for the screening and prevention of UC in clinical practice. In addition, they could serve as potential candidate molecules for elucidating the mechanisms underlying UC and for identifying suitable drug targets.