# Unveiling Shared Genetic Architectures and Causality: Intestinal Diseases and Neurological Diseases

## TL;DR

This study explores the genetic links and potential causal relationships between intestinal and neurological diseases using genome-wide data, revealing shared genetic factors and immune system involvement.

## Contribution

The study identifies novel shared genetic loci and causal relationships between intestinal and neurological diseases using multi-omic approaches.

## Key findings

- Positive global genetic correlations were found between irritable bowel syndrome and epilepsy, and between irritable bowel syndrome and stroke.
- Local genetic correlations were identified between ulcerative colitis and multiple sclerosis in a specific genomic region.
- Causal effects of Crohn's disease on Parkinson's disease were detected using Mendelian randomization.

## Abstract

The “gut–brain axis” provides a theoretical foundation for the connection between intestinal and neurological diseases, but whether this reflects a shared genetic etiology or causal relationships exist remains unclear.

We used genome‐wide association study summary data from FinnGen and UK Biobank to investigate the genetic correlations and causal relationships between three intestinal diseases and six neurological diseases.

We observed positive global genetic correlations between irritable bowel syndrome and epilepsy (r
g = 0.429, p = 1.53 × 10−2), and stroke (r
g = 0.368, p = 2.56×10−2). Upon dividing the whole genome into 1703 independent regions, local genetic correlations were identified in a region between ulcerative colitis and multiple sclerosis (Chr6: 31571218–32682664). We also identified 12 novel pleiotropic SNPs shared between intestinal and neurological diseases, as well as a functional gene shared between ulcerative colitis and multiple sclerosis. SNP heritability enrichment analysis indicated that ulcerative colitis and multiple sclerosis have enrichment in several immune cells. Two‐sample Mendelian randomization indicated the causal effect of Crohn's disease on Parkinson's disease (FDR = 1.34 × 10−2, OR = 1.092). The methylome Mendelian randomization analysis also showed causal relationships between several intestinal and neurological diseases.

Through comprehensive and systematic statistical analysis, we identified the global and local genetic correlations and causal relationships between several intestinal and neurological diseases and discovered shared pleiotropic loci and genes between them. Furthermore, the consistent SNP heritability enrichment observed in immune cells also indicated the crucial role of the immune system in the “gut–brain axis.”

We analyzed the genetic correlations and causal relationships between intestinal and neurological diseases, identifying global and local genetic associations between them. We identified shared pleiotropic loci and genes, as well as SNP heritability enrichments in tissues and cells. We also revealed potential causal relationships between these diseases from a multi‐omic perspective.