Genetics

This blog post reviews Ma et al.’s integrative framework for translating multiple sclerosis (MS) GWAS signals into actionable biology by mapping noncoding risk variants onto cell-type-specific regulatory DNA and three-dimensional chromatin contacts. By combining enrichment analyses across open chromatin, histone marks, and ENCODE cis-regulatory elements with H-MAGMA gene assignment using promoter capture Hi-C/HiChIP, the study highlights B cells and monocytes as dominant peripheral mediators of genetic risk and identifies microglia as the primary CNS-resident cell type implicated by MS genetics. The post also summarizes how cell-specific polygenic risk scores derived from these annotations associate with MS susceptibility and brain white matter volume, underscoring a coherent regulatory narrative that connects genetic architecture to immune pathways and potential therapeutic prioritization.