Shared Plasma Metabolites Mediate Causal Effects of Metabolic Diseases on Colorectal Cancer: A Two-Step Mendelian Randomization Study.

ABSTRACT: Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify the plasma metabolites mediating these effects; and (3) explore downstream regulatory genes and druggable targets. Methods: Using linkage disequilibrium score regression and two-sample Mendelian randomization, we assessed the causal relationships between each metabolic trait and CRC. A total of 1091 plasma metabolites and 309 metabolite ratios were identified and analyzed for mediating effects by a two-step MR approach. Colocalization analyses

SUBMITTER: Shi X 

PROVIDER: S-EPMC12561098 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature