A Multi-omics approach to identify and validate shared genetic architecture in rheumatoid arthritis, multiple sclerosis, and type 1 diabetes: integrating GWAS, GEO, MSigDB, and scRNA-seq data

The notable comorbidity among autoimmune diseases underscores their shared genetic underpinnings, particularly evident in rheumatoid arthritis (RA), type 1 diabetes (T1D), and multiple sclerosis (MS). However, the exact components and mechanisms of this shared genetic structure remain poorly understood. Here we show that ROMO1 is a key shared genetic component among RA, MS, and T1D. Using differential gene expression (DGE) and LASSO regression analyses of bulk RNA-seq data from whole blood tissues, we identified ROMO1 as a potential shared genetic factor. A multi-sample analysis with external Gene Expression Omnibus (GEO) data revealed ROMO1’s consistent association with immune cell patterns across tissues in all three diseases. Single-gene Gene Set Enrichment Analysis (GSEA) suggested ROMO1’s involvement in the reactive oxygen species (ROS) pathway, which was further substantiated by conjoint analysis with 256 ROS pathway-related genes(ROSGs) from Molecular Signatures Database (MSigDB). Single-gene Receiver Operating Characteristic (ROC) analysis highlighted ROMO1’s potential as a disease biomarker. Single-cell RNA sequencing (scRNA-seq) analysis showed significantly altered ROMO1 expression in monocytes and other immune cells compared to healthy control (HC). Immune infiltration analysis revealed ROMO1’s significant association with monocytes across all three diseases. Furthermore, two-sample Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) data demonstrated that ROMO1 could regulate epitopes on monocytes, potentially lowering autoimmune disease risk. Our findings clarify the importance of ROMO1 in the shared genetic architecture of RA, MS, and T1D, and its underlying mechanism in disease development. © The Author(s) 2025.