AUTHOR=Hong Xiangxiang , Wang Xin , Rang Xinming , Yin Xinyue , Zhang Xuemei , Wang Rui , Wang Duo , Zhao Tingting , Fu Jin 

TITLE=The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren’s Syndrome Analyzed by Bioinformatics Based on GWAS and Transcriptome Data

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.857014

DOI=10.3389/fimmu.2022.857014

ISSN=1664-3224

ABSTRACT=Abstract
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 bioinformatic analysis based on GWAS and transcriptome data from GWAS catalog and GEO database. Pathway enrichment, GO analysis, and protein-protein interaction analysis for susceptibility genes and DEGs were performed. The drugs targeting common pathways/genes were obtained through CTD, DrugBank and DGI databases. 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、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 519 drugs. “JAK-STAT signaling pathway” was included in common susceptibility pathways and common risk pathways at the same time. There were 136 overlaps including JAK-STAT inhibitors between agents form 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 which 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 basis of comorbidity of MS with SS. Moreover, JAK-STAT inhibitors was a potential therapy for MS and SS, especially comorbidity of them.