Background Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are recognized as interconnected immune disorders, necessitating comprehensive genetic analysis. Methods The research employed genome-wide association study (GWAS) data pertinent to IBD and PSC. Initially, linkage disequilibrium score regression alongside SUPERGNOVA was utilized to assess their genetic correlation. The genetic overlap between these two conditions was subsequently evaluated using the conditional/conjunctional false discovery rate (cond/conjFDR) approach. Shared loci pertinent to IBD and PSC were discerned through both conjFDR and multitrait analysis of GWAS (MTAG) techniques. Finally, transcriptome-wide association studies were executed at the tissue level to investigate enriched tissues and expressed genes. Results A substantial overall correlation was identified at the genome-wide level between IBD (including Crohn’s disease and ulcerative colitis) and PSC. Locally, correlations were prominent as both diseases exhibited enrichment across various chromosomes, with chromosome 9 being particularly noteworthy. The conditional quantile–quantile plot derived from the conjFDR analysis indicated genetic overlap between the two diseases. Using an integrated approach involving conjFDR and MTAG analyses, 15, 12, and 6 shared loci were detected for IBD, Crohn’s disease, and ulcerative colitis with PSC, respectively. Furthermore, concurrent enrichment of IBD and PSC was found in seven tissues (spleen, terminal ileum of the small intestine, whole blood, lung, Epstein–Barr virus-transformed lymphocytes, transverse colon, and adipose visceral omentum). Conclusion This study provides genetic evidence for the comorbidity of IBD and PSC, enhancing our understanding of the pathophysiological aspects of both diseases.
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