# Causal Inference and Shared Molecular Pathways in Crohn’s Disease, Celiac Disease, and Ankylosing Spondylitis: Integrative Mendelian Randomization and Transcriptomic Analysis

## TL;DR

This study finds shared genetic and immune mechanisms among Crohn’s disease, celiac disease, and ankylosing spondylitis, suggesting new treatment possibilities.

## Contribution

The study identifies three shared hub genes and a potential therapeutic agent through integrative causal and transcriptomic analysis.

## Key findings

- Three hub genes (P2RY8, ITGAL, GPR65) are upregulated across all three diseases and validated in independent datasets.
- Bidirectional Mendelian randomization shows significant causal associations between each disease pair.
- Trichostatin A is highlighted as a potential therapeutic agent based on regulatory and molecular analyses.

## Abstract

This study explored the causal and molecular overlap among Crohn’s disease (CD), celiac disease (CeD), and ankylosing spondylitis (AS). Bidirectional Mendelian randomization revealed significant causal associations between each disease pair. Transcriptomic analyses identified three consistently upregulated hub genes—P2RY8, ITGAL, and GPR65—across all conditions, which were validated in independent datasets and inflammatory cell models. Functional enrichment suggested these genes are involved in immune signaling and mucosal inflammation. Regulatory network and molecular docking analyses further highlighted Trichostatin A as a potential therapeutic agent. These findings reveal shared genetic and immune-related mechanisms, offering novel targets for cross-disease treatment strategies.