Causal pathways in Lymphoma: The role of serum metabolites and immune cells determined by Mendelian randomization.

Background: Prior research has demonstrated significant roles of metabolites and immune cells in the progression of lymphoma. Mendelian randomization studies have been conducted to assess the causal relationships among serum metabolites, immune cells, and lymphoma, further exploring the mediating role of serum metabolites.

Methods: Using summary-level data from genome-wide association studies (GWAS), we applied two-sample Mendelian randomization (TSMR) techniques, including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, Simple Mode, and Weighted Mode. These methods were employed to examine the causal links between genetically determined serum metabolites, immune cells, and six types of lymphoma. Additionally, reverse MR analysis investigated reverse causality, and two-step MR quantified the proportion of lymphoma effects mediated by immune cells through serum metabolites. MR-Egger regression and leave-one-out sensitivity tests evaluated the stability and reliability of our findings.

Results: The study pinpointed specific serum metabolites and immune cell types causally related to six lymphoma variants. Serum metabolites were identified as mediators in the relationship between immune cells and lymphoma. The two-step Mendelian randomization confirmed this mediated causal relationship, with sensitivity analyses supporting the results' reliability and lack of pleiotropy.

Conclusion: The study establishes a causal connection between immune cells and lymphoma, partially mediated by serum metabolites, although the majority of the influence remains undefined. Future research should explore additional potential mediators. Clinically, there should be an increased focus on immune cells biomarkers for lymphoma patients. These results offer valuable insights for identifying lymphoma biomarkers and potential therapeutic targets.