A Multitrait Analysis of Genome-Wide Association Study Reveals the Shared Genetic Architecture Between Inflammatory Bowel Disease and Ankylosing Spondylitis.

BACKGROUND

Clinical evidence indicates that inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) often co-occur, but their genetic mechanisms remain unclear. Our objective is to explore the genetic relationship between IBD and AS.

METHODS

Using large-scale summary statistics from genome-wide association study (GWAS), we investigated the shared genetic architecture between IBD, including ulcerative colitis (UC) and Crohn's disease (CD), and AS. Starting with genetic correlation, we then examined shared genetic structures and genes, followed by causal inference, and explored potential functional genes and biological pathways in tissue and cell types.

RESULTS

We observed a positive genetic correlation between IBD and AS (IBD-AS: r g  = 0.252, p=3.78e - 06; CD-AS: r g  = 0.268, p=5.19e - 06; UC-AS: r g  = 0.171, p=6.64e - 03). Multitrait analysis of GWAS (MTAG) and cross-phenotype association analysis (CPASSOC) identified 24 pleiotropic single-nucleotide polymorphisms (SNPs) across three trait pairs. Gene association analysis from three methods collectively identified eight shared functional genes for IBD and AS. Shared tissue-specific genetic enrichment was found in lung, spleen, small intestine, and whole blood tissues. Additionally, common enrichment was observed in specific cell types, such as T and B cells. Bidirectional Mendelian randomization (MR) analysis revealed no causal relationship between the two conditions.

CONCLUSIONS

This study confirms the genetic correlation between IBD and AS, identifies their shared genetic architecture and biological pathways, providing strong evidence for the genetic comorbidity of IBD and AS. These findings offer directions for future research.