This study used multi-source transcriptomic data combined with Mendelian randomization analyses, including differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and Mendelian randomization, to identify eight candidate genes that were significantly negatively associated with bladder cancer risk: LIMS2, TP53INP2, IRAK3, STX2, CYP27A1, IL11RA, KCNMB1, and PDLIM7. Here, STX2 is linked to urinary bladder cancer.