Assessing the associations of blood metabolites with myelodysplastic syndrome: A bidirectional mendelian...

Metabolic disorders are a hallmark feature of cancer. However, evidence regarding the causality of circulating metabolites in promoting or preventing myelodysplastic syndrome (MDS) is currently insufficient. We conducted a bidirectional Mendelian randomization analysis (MR) to assess the causal relationship between genetically proxied 1400 blood metabolites and MDS.

In this study, we employed a bidirectional MR framework to explore the potential causal links between blood metabolites and the risk of MDS. Data on blood metabolites were derived from a comprehensive genome-wide association study (GWAS) dataset of European origin. Initial analyses used MDS GWAS data from the GWAS catalog. The pleiotropy, and heterogeneity analysis were applied to confirm the stability of the MR estimates.

In a survey of 1400 metabolites, four exhibited statistical significance (P < 0.05) in an inverse variance weighted (IVW) model. Levels of Alpha-hydroxyisovalerate [odds ratio (OR) = 3.157, p < 0.001], Pregnenediol disulfate (C21H34O8S2) [OR = 2.805, p < 0.001] and 1-linoleoyl-GPG (18:2) [OR = 2.756, p < 0.001] were positively causally associated with MDS, while X-18345 [OR = 0.360, p < 0.001] was negatively associated with MDS. On the contrary, MDS did not lead to significant alterations in the levels of the aforementioned four blood metabolites.

In this study, a possible causal relationship was established between four blood metabolites and MDS. Among these, three specific blood metabolites were identified as causal factors in the development of MDS and were confirmed as risk factors. Interestingly, an unknown blood metabolite emerged as a protective factor.