Image_2_The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren’s Syndrome Analyzed by Bioinformatics Based on GWAS and Transcripto.png (644.58 kB)
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Image_2_The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren’s Syndrome Analyzed by Bioinformatics Based on GWAS and Transcriptome Data.png

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posted on 09.03.2022, 04:03 authored by Xiangxiang Hong, Xin Wang, Xinming Rang, Xinyue Yin, Xuemei Zhang, Rui Wang, Duo Wang, Tingting Zhao, Jin Fu
Objective

This study aimed to explore the shared mechanism and candidate drugs of multiple sclerosis (MS) and Sjögren’s syndrome (SS).

Methods

MS- and SS-related susceptibility genes and differentially expressed genes (DEGs) were identified by bioinformatics analysis based on genome-wide association studies (GWAS) and transcriptome data from GWAS catalog and Gene Expression Omnibus (GEO) database. Pathway enrichment, Gene Ontology (GO) analysis, and protein–protein interaction analysis for susceptibility genes and DEGs were performed. The drugs targeting common pathways/genes were obtained through Comparative Toxicogenomics Database (CTD), DrugBank database, and Drug–Gene Interaction (DGI) Database. The target genes of approved/investigational drugs for MS and SS were obtained through DrugBank and compared with the common susceptibility genes.

Results

Based on GWAS data, we found 14 hub common susceptibility genes (HLA-DRB1, HLA-DRA, STAT3, JAK1, HLA-B, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB5, HLA-DPA1, HLA-DPB1, TYK2, IL2RA, and MAPK1), with 8 drugs targeting two or more than two genes, and 28 common susceptibility pathways, with 15 drugs targeting three or more than three pathways. Based on transcriptome data, we found 3 hub common DEGs (STAT1, GATA3, PIK3CA) with 3 drugs and 10 common risk pathways with 435 drugs. “JAK-STAT signaling pathway” was included in common susceptibility pathways and common risk pathways at the same time. There were 133 overlaps including JAK-STAT inhibitors between agents from GWAS and transcriptome data. Besides, we found that IL2RA and HLA-DRB1, identified as hub common susceptibility genes, were the targets of daclizumab and glatiramer that were used for MS, indicating that daclizumab and glatiramer may be therapeutic for SS.

Conclusion

We observed the shared mechanism of MS and SS, in which JAK-STAT signaling pathway played a vital role, which may be the genetic and molecular bases of comorbidity of MS with SS. Moreover, JAK-STAT inhibitors were potential therapies for MS and SS, especially for their comorbidity.

History

References