Genetic, Transcriptomic, and Epigenomic Insights into Sjögren's Disease: An Integrative Network Investigation and Immune Diseases Comparison

Authors

Nitesh Enduru
Astrid M Manuel
Zhongming Zhao

Language

English

Publication Date

5-13-2025

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms26104637

PMID

40429780

PMCID

PMC12111751

PubMedCentral® Posted Date

5-13-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Sjögren's disease (SjD) is a systemic autoimmune disorder primarily causing dry eyes and mouth. It frequently overlaps with other autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic basis of SjD remains underexplored, limiting our understanding of its connections to other immune-mediated conditions. In this study, we aimed to identify gene networks associated with SjD through the integration of genetic, transcriptomic, and epigenomic data. We further compared the genetic factors of SjD with other immune-mediated diseases. We analyzed genome-wide association studies (GWAS) summary statistics, DNA methylation, and transcriptomic data using our in-house network-based methods, dmGWAS and EW_dmGWAS, to identify key gene modules associated with SjD. In dmGWAS analysis, discovery and evaluation datasets were used to identify consensus results. We conducted gene-set, cell-type, and disease-enrichment analyses on significant gene modules and explored potential drug targets. Genetic correlations and Mendelian randomization were applied to assess SjD's link with 17 other AIDs and 16 cancer types. dmGWAS identified 207 and 211 gene modules in the discovery and evaluation phases, respectively, while EW_dmGWAS detected 886 modules. Key modules highlighted 55 genes (discovery), 52 genes (evaluation), and 59 genes (EW_dmGWAS), with at least 50 genes from each analysis linked to AIDs and cancer. Enrichment analyses confirmed their relevance to immune and oncogenic pathways. We pinpointed four candidate drug targets associated with AIDs. We developed a novel integrative omics approach to identify potential genetic markers of SjD and compared them with AIDs and cancers. Our approach can be similarly applied to other disease studies.

Keywords

Humans, Sjogren's Syndrome, Gene Regulatory Networks, Transcriptome, Genome-Wide Association Study, DNA Methylation, Epigenomics, Genetic Predisposition to Disease, Gene Expression Profiling, Epigenesis, Genetic, autoimmune disease, genome-wide association studies, pleiotropy, Mendelian randomization, genetic correlation, drug target

Published Open-Access

yes

Recommended Citation

Nitesh Enduru, Astrid M Manuel, and Zhongming Zhao, "Genetic, Transcriptomic, and Epigenomic Insights into Sjögren's Disease: An Integrative Network Investigation and Immune Diseases Comparison" (2025). Faculty, Staff and Student Publications. 584.
https://digitalcommons.library.tmc.edu/uthshis_docs/584