Autoimmunity, Journal Year: 2025, Volume and Issue: 58(1)
Published: March 26, 2025
Autoimmune diseases (ADs), such as Graves' disease (GD), Hashimoto's thyroiditis (HT), psoriasis, systemic lupus erythematosus (SLE), and type 1 diabetes (T1D), involve complex immune inflammatory responses. This study employed Mendelian randomization (MR) analysis using genome-wide association (GWAS) data to examine the causal relationships among 91 circulating proteins, 41 cytokines, 211 gut microbiota, 731 cell traits in relation ADs. Additionally, we integrated mediation bioinformatics analyses, including protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes Genomes (KEGG) pathway analysis. Subnetwork discovery key protein identification were performed Molecular Complex Detection (MCODE) plugin, alongside colocalization drug target exploration identify potential mechanisms. MR identified significant between various microbiota species, cells, ADs, with certain retaining significance after false rate (FDR) correction. Mediation demonstrated that proteins mediate pathogenic pathways linking cells psoriasis thyroiditis. PPI analyses highlighted 22 involved while subnetwork 15 central proteins. Fms-related tyrosine kinase 3 ligand (FLT3LG) exhibited strong evidence. docking confirmed several viable targets. comprehensive multi-omics advances our understanding identifies novel therapeutic targets, offers valuable insights for developing new treatment strategies.
Language: Английский