Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.693142
Keywords
multiple autoimmune diseases; shared gene regulatory mechanisms; non-HLA module; HLA module; immune pathways; cancer pathways
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Integrating various data resources, the study identified genes regulated by both pleiotropic and non-pleiotropic SNPs, revealing complex interactions between shared and disease-specific genes, which co-occur within the same biological pathways.
Autoimmune diseases (AiDs) are complex heterogeneous diseases characterized by hyperactive immune responses against self. Genome-wide association studies have identified thousands of single nucleotide polymorphisms (SNPs) associated with several AiDs. While these studies have identified a handful of pleiotropic loci that confer risk to multiple AiDs, they lack the power to detect shared genetic factors residing outside of these loci. Here, we integrated chromatin contact, expression quantitative trait loci and protein-protein interaction (PPI) data to identify genes that are regulated by both pleiotropic and non-pleiotropic SNPs. The PPI analysis revealed complex interactions between the shared and disease-specific genes. Furthermore, pathway enrichment analysis demonstrated that the shared genes co-occur with disease-specific genes within the same biological pathways. In conclusion, our results are consistent with the hypothesis that genetic risk loci associated with multiple AiDs converge on a core set of biological processes that potentially contribute to the emergence of polyautoimmunity.
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