Genetics

This blog post reviews a multi-omic framework that integrates MS GWAS signals with cell-type-specific regulatory annotations and 3D chromatin interaction maps to pinpoint the immune and CNS cell programs most likely to mediate inherited risk. By combining enrichment analyses of active cis-regulatory elements with H-MAGMA gene mapping in B cells, monocytes, and microglia, the article builds mechanistic hypotheses that connect noncoding variants to target genes and pathways. It then validates these hypotheses quantitatively using cell-specific polygenic risk scores across large biobank data and an independent clinical cohort, showing that distinct “cell-type genetic burdens” relate not only to MS case status but also to MRI-derived white matter measures and relapse activity.