Single cell sequencing analysis identifies genetics-modulated ORMDL3 + cholangiocytes having higher metabolic effects on primary biliary cholangitis

Primary biliary cholangitis (PBC) is a classical autoimmune disease, which is highly influenced by genetic determinants. Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with PBC susceptibility. However, the effects of genetic determi...

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Bibliographic Details
Published in:Journal of nanobiotechnology 2021-12, Vol.19 (1), p.406-21, Article 406
Main Authors: Xiang, Bingyu, Deng, Chunyu, Qiu, Fei, Li, Jingjing, Li, Shanshan, Zhang, Huifang, Lin, Xiuli, Huang, Yukuan, Zhou, Yijun, Su, Jianzhong, Lu, Mingqin, Ma, Yunlong
Format: Article
Language:English
Subjects:
Autoimmune diseases
Biliary Tract - cytology
Biliary Tract - metabolism
Cells, Cultured
Cholangitis
Computer applications
Cytokines
Dendritic cells
Diabetes
Dimethylargininase
Etiology
Gene expression
Gene loci
Genes
Genetic aspects
Genetics
Genome-Wide Association Study
Genomes
GWAS
Health aspects
Hepatocytes
Humans
Immune response
Immunomodulation
Inflammatory bowel disease
Information processing
Kinases
Liver
Liver cells
Liver Cirrhosis, Biliary - genetics
Liver Cirrhosis, Biliary - metabolism
Liver diseases
Lupus
Macrophages
Membrane Proteins - genetics
Membrane Proteins - metabolism
Metabolism
Microenvironments
Monocytes
ORMDL3
PBC
Regulation
Rheumatoid arthritis
Risk analysis
Risk factors
Risk genes
RNA-Seq
Sequence analysis
Signal transduction
Single cell sequencing analysis
Single-Cell Analysis - methods
Statistical analysis
Subpopulations
Vascular endothelial growth factor
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Summary:Primary biliary cholangitis (PBC) is a classical autoimmune disease, which is highly influenced by genetic determinants. Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with PBC susceptibility. However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear. We constructed a powerful computational framework to integrate GWAS summary statistics with scRNA-seq data to uncover genetics-modulated liver cell subpopulations for PBC. Based on our multi-omics integrative analysis, 29 risk genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. By combining GWAS summary statistics with scRNA-seq data, we found that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals (Permuted P 
ISSN:1477-3155
1477-3155
DOI:10.1186/s12951-021-01154-2