Integrating Genomic, eQTL, and Mendelian Randomization Analyses to Identify Microglial Drug Targets in Multiple Sclerosis.

ABSTRACT: Multiple sclerosis (MS) is an autoimmune disease characterised by neuroinflammation and neurodegeneration. This study investigates genetic and immunological factors in MS, focusing on microglial regulation. We analysed differentially expressed genes using RNA sequencing from MS lesions (GSE108000) and plaques (GSE227781), validated with cis-eQTL analysis, and integrated Mendelian randomisation (MR), SMR, co-localisation, methylation, and protein-protein interaction (PPI) analyses to assess causal effects on MS risk. We identified five genes-ARHGAP25, HLA-DRB1, MERTK, MS4A6A, and SYK-linked to MS susceptibility. MR revealed that elevated levels of ARHGAP25 (OR = 1.45), HLA-DRB1 (OR = 2.24), MERTK (OR = 1.10), MS4A6A (OR = 1.15), and SYK (OR = 1.13) increased MS risk. SMR confirmed a causal

SUBMITTER: Yan W 

PROVIDER: S-EPMC12618184 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature