Causal effects of genetically determined blood metabolites on multiple myeloma: a Mendelian randomization study

Abstract

AbstractPrevious studies have shown that metabolites play an important role in phenotypic regulation. However, the causal relationship between metabolites and multiple myeloma has not been adequately investigated. Here, we attempt to explore the causal effects of genetically determined blood metabolites on multiple myeloma. The large-scale public blood metabolites and multiple myeloma datasets from independently published genome-wide association studies (GWAS) were used to explore the causal relationship between each genetically determined blood metabolite and multiple myeloma through inverse variance weighted (IVW), weighted median, MR-Egger and mode-based estimation methods. Sensitivity tests were performed to evaluate the stability and reliability of the results by MR-Egger regression and leave-one-out methods. Metabolic pathway analysis was further explored using filtered data. Statistical analyses were all performed in R. Among 452 metabolites, ten known metabolites and three unknown metabolites had significant causal relationship with multiple myeloma (P < 0.05). Four known metabolites, 3-methyl-2-oxovalenate, oxidized bilirubin, isovalerylcarnitine and glutamine carnitine, reached statistical significance in IVW models. Metabolic pathways analysis identified four significant pathways. The occurrence of multiple myeloma may have a causal relationship with these four metabolites, and there are four metabolic pathways that are also related to the occurrence of multiple myeloma. This can provide new ideas for exploring early screening and treatment of multiple myeloma.