# Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI

## TL;DR

This study finds that mTOR gene activity is linked to BMI, suggesting mTOR inhibitors could help reduce body weight beyond cancer treatment.

## Contribution

The study identifies a causal link between mTOR gene expression and BMI, opening new non-cancer applications for mTOR inhibitors.

## Key findings

- mTOR gene expression is causally linked to body mass index (BMI).
- mTOR-related vulnerabilities in metabolites, immune traits, and gut microbiota are associated with BMI.
- mTOR inhibitors may have potential for non-cancer applications like weight management.

## Abstract

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.