# Cross-tissue transcriptome-wide association identify novel T1D susceptibility genes and drug candidates

## TL;DR

This study identifies new genes linked to type 1 diabetes and suggests potential drug candidates for treatment.

## Contribution

The study discovers seven novel T1D susceptibility genes and proposes three druggable targets with specific compounds.

## Key findings

- Ten genes associated with T1D risk were identified, seven of which are novel.
- Three genes (ELK4, SULT1A2, and WFS1) were prioritized as druggable targets.
- Potential therapeutic agents COMPOUND 5G and DCLK1-IN-1 were identified through computational analyses.

## Abstract

The genetic mechanisms underlying type 1 diabetes (T1D) remain incompletely understood, limiting the development of targeted therapies.

We performed an integrative genetic analysis to identify T1D susceptibility genes and therapeutic targets. This included a cross-tissue transcriptome-wide association study (TWAS) to pinpoint genes with genetically predicted expression associated with T1D risk, followed by Mendelian randomization to infer causality. Identified genes were further characterized through pathway, cell-type enrichment, drug prediction, molecular docking, and phenome-wide association studies.

We identified ten genes associated with T1D risk, seven of which (ELK4, PHACTR4, MAST2, ST7L, C1orf216, SULT1A2, and WFS1) are novel candidates in this context. Three genes (ELK4, SULT1A2, and WFS1) were prioritized as druggable targets, with COMPOUND 5G and DCLK1-IN-1 emerging as potential therapeutic agents through computational analyses.

Our study reveals novel genetic associations and immune-related pathways in T1D pathogenesis, and proposes specific genes and compounds as promising focal points for future mechanistic and therapeutic exploration.