Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI

Background: Although mTOR has long been regarded as a promising target for cancer treatment, the efficacy of mTOR inhibitors in most clinical trials has been rather limited. Nevertheless, their favorable safety profile has opened up opportunities for drug repurposing, even as their potential applications across various diseases remain largely unexplored. Methods: We performed an MR-PheWAS analysis across 1431 phenotypes to explore drug repurposing opportunities. We analyzed GWAS data of 452 plasma metabolites, 731 immune traits, and 412 gut microbiota to uncover potential mechanisms for the causal link between the mTOR gene and body mass index (BMI). Results: A causal link between mTOR gene expression and BMI has been established. Additionally, mTOR-related vulnerabilities associated with BMI, including alterations in metabolites, immune traits, and gut microbiota, were identified. Conclusions: The identified causal relationship between mTOR and BMI suggests novel potential non-cancer applications for mTOR inhibitors.