Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis

作者：Wentao Huang, Rui Jiang, Sitao Li, Ruijie Zeng, Li Yang, Yajie Zhang, Shuangshuang Tong, Yanlin Lyu, Jiaxuan Wang, Qizhou Lian, Felix W. Leung, Ruibang Luo, Weihong Sha, Hao Chen · 发表于：JHEP Reports · 年份：2024 · DOI：10.1016/j.jhepr.2024.101037 · 被引用次数：22 · 研究领域：Liver Diseases and Immunity、Inflammatory Bowel Disease、Single-cell and spatial transcriptomics

Background & Aims: Inflammatory bowel disease (IBD) is commonly associated with extraintestinal complications, including autoimmune liver disease. The co-occurrence of IBD and primary biliary cholangitis (PBC) has been increasingly observed, but the underlying relationship between these conditions remains unclear. Methods: Using summary statistics from genome-wide association studies (GWAS), we investigated the causal effects between PBC and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). We also analyzed the shared genetic architecture between IBD and PBC using data from GWAS, bulk-tissue RNA sequencing, and single cell RNA sequencing, and explored potential functional genes. Result: . Shared tissue-specific heritability enrichment was identified for PBC and IBD (including CD and UC) in lung, spleen, and whole-blood samples. Furthermore, shared enrichment was observed of specific cell types (T cells, B cells, and natural killer cells) and their subtypes. Nine functional genes were identified based on summary statistics-based Mendelian randomization. Conclusions: This study detected shared genetic architecture between IBD and PBC and demonstrated a stable causal relationship of genetically predicted PBC on the risk of IBD. These findings shed light on the biological basis of comorbidity between IBD and PBC, and have important implications for intervention and treatment targets of these two diseases simultaneously. Impact and Implications: The discovery of nov...