Cell Type-Specific Intralocus Interactions Reveal Oligodendrocyte Mechanisms in MS.

ABSTRACT: Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients may still face progressive disability because of failure of myelin regeneration and loss of neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which a disease allele exerts a pathogenic effect. Applying this approach to MS risk loci, we pinpoint likely pathogenic cell types for 70%. In addition to T cell loci, we unexpectedly identified myeloid- and CNS-specific risk loci, including two sites that dysregulate transcriptional pause release in oligodendrocytes. Functional studies demonstrated inhibition of transcriptional

SUBMITTER: Factor DC 

PROVIDER: S-EPMC7426147 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature