A gene regulatory network approach harmonizes genetic and epigenetic signals and reveals repurposable drug candidates for multiple sclerosis.

ABSTRACT: Multiple sclerosis (MS) is a complex dysimmune disorder of the central nervous system. Genome-wide association studies (GWAS) have identified 233 genetic variations associated with MS at the genome-wide significant level. Epigenetic studies have pinpointed differentially methylated CpG sites in MS patients. However, the interplay between genetic risk factors and epigenetic regulation remains elusive. Here, we employed a network model to integrate GWAS summary statistics of 14 802 MS cases and 26 703 controls with DNA methylation profiles from 140 MS cases and 139 controls and the human interactome. We identified differentially methylated genes by aggregating additive effects of differentially methylated CpG sites within promoter regions. We reconstructed a gene regulatory network (GRN) usi

SUBMITTER: Manuel AM 

PROVIDER: S-EPMC9991005 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature