Causal relationship between serum metabolites and chronic myeloid leukemia: A bidirectional Mendelian randomization study.

Previous studies have found a link between serum metabolite levels and chronic myeloid leukemia (CML), yet their exact causal relationship remains unexplored. Using genome-wide association datasets, we conducted bidirectional Mendelian randomization (MR) analyses to explore the potential causal relationship between 486 serum metabolites and CML. We conducted sensitivity analysis to assess the presence of heterogeneity and pleiotropy. Our Mendelian randomization analysis identified 20 metabolites exerting significant causal effects on CML, including 19 known and 1 unidentified metabolite. Among the 19 identified metabolites, 10 metabolites exhibit a risk effect in CML, whereas 9 manifested a protective effect. Notably, the amino acid metabolite 4-methyl-2-oxopentanoate displayed the strongest positive causal relationship with CML. The CML-associated metabolites were predominantly enriched in the following metabolic pathways: caffeine metabolism, glycerolipid metabolism, glycerophospholipid metabolism, and valine, leucine, and isoleucine biosynthesis. These findings advance our understanding of metabolic interactions in CML, providing critical insights for diagnosis and guiding strategies for prevention and treatment.