Gene Set Enrichment Analysis Detected Immune Cell-Related Pathways Associated with Primary Sclerosing Cholangitis
BIOMED RESEARCH INTERNATIONAL(2022)
摘要
Aim. To explore various immune cell-related causal pathways for primary sclerosing cholangitis (PSC). Methods. Immune cell related pathway association study was conducted via integrative analysis of PSC GWAS summary and five immune cell-related eQTL datasets. The GWAS summary data of PSC was driven from 4,796 PSC cases and 19,955 healthy controls. The eQTL datasets of CD4+ T cells, CD8+ T cells, B cells, natural killer cells (NK), monocytes, and peripheral blood cells (PB) were collected from recently eQTL study. The PSC GWAS summary dataset was first aligned with eQTL datasets of six blood cells to obtain the GWAS summary data at overlapped eQTL loci, separately. For each type of cell, the obtained PSC GWAS summary dataset of eQTLs was subjected to pathway enrichment analysis. 853 biological pathways from Kyoto Encyclopedia of Genes and Genomes, BioCarta, and Reactome pathway databases were analyzed. Results. We identified 36 pathways for B cells, 33 pathways for CD4+ T cells, 28 pathways for CD8+ T cells, 33 pathways for monocytes (MN), 35 pathways for NK cells, and 33 for PB cells (all empirical P values < 5.0x10(-5)). Comparing the pathway analysis results detected 25 pathways shared by five immune cells, such as KEGG_CELL_ADHESION_MOLECULES_CAMS (P value < 5.0x10(-5)) and REACTOME_MHC_CLASS_II_ANTIGEN_ PRESENTATION (P value < 5.0x10-5). Several cell-specific pathways were also identified, including BIOCARTA_INFLAM_PATHWAY (P value < 5x10(-5)) for B cell. Conclusion. Our study holds potential to identify novel candidate causal pathways and provides clues for revealing the complex genetic mechanism of PSC.
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关键词
immune,cell-related
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