Related Experiment Video
Updated: Sep 17, 2025
Investigating Target Gene Function in a CD40 Agonistic Antibody-induced Colitis Model using CRISPR/Cas9-based Technologies
Published on: June 2, 2021
Causal effects of brain subregion gene expression on inflammatory bowel diseases revealed by Mendelian randomization
Yuan Li1, Yao Wang1, Simeng Chen1
1Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Abstract:
Inflammatory Bowel Diseases (IBDs), including Ulcerative Colitis (UC) and Crohn's Disease (CD), are chronic gastrointestinal disorders. The gut-brain axis integrates various signals, but its impact on IBD is unclear. Using Mendelian Randomization, we evaluated causal relationships between 13 brain subregions and colon expression quantitative trait loci (eQTLs) with IBDs. Trans-omics analysis, integrating brain, CD and UC intestine single-cell RNA sequencing and genomic eQTLs, identified cellular sources of key genes. Phenome-Wide Association Studies (PheWAS) filtered phenotype associations of leading SNPs. Brain eQTLs showed meaningful associations with IBD susceptibility, with consistent patterns observed across multiple independent cohorts (IIBDGC, UKB, and FinnGen). However, correlation analysis revealed that eQTL sample sizes significantly influence the detection of significant associations (r = 0.53-0.90), indicating that direct quantitative comparisons between tissues should be interpreted cautiously. Multiple brain regions, including the cerebellum, cerebellar hemisphere, and cortex, demonstrated notable associations with IBD. Exploratory analysis identified genes CCDC88B, NAAA and NAGLU showing putative positive causal associations with IBD susceptibility in both brain and colon tissues, whereas CWC15 exhibited an inverse relationship. Stringent Bonferroni correction validated CCDC88B and NAGLU as robust candidates across multiple tissues and IBD subtypes. Single-cell RNA sequencing identified dendritic cells and epithelial cells as sources of NAAA and CWC15, respectively, enriched in inflammatory pathways. PheWAS showed leading SNPs associated with metabolic dysfunction, immune disorders, and brain imaging measures. This study demonstrates meaningful brain-gut axis involvement in IBD pathogenesis while acknowledging methodological limitations in cross-tissue comparisons. The identified candidate genes and cellular mechanisms provide new insights for understanding IBD susceptibility and potential therapeutic targets.
Related Concept Videos
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...