Multiple sclerosis immunogenetics: moving to multi-omics single-cell resolution

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that affects 2.5 million people worldwide and leads to important physical and cognitive disability with typical onset during young adulthood. Over the past years, the Laboratory for Neuroimmunology (KU Leuven) identified 233 MS genetic risk factors, which are shared with other autoimmune but not neurological disorders and implicate specific immune cells in the pathogenesis and disease mechanisms of MS. They also demonstrated that genetic factors for heterogeneity are different from those for susceptibility, and identified genetic and environmental factors, as well as biomarkers underlying heterogeneity in disease activity and progression. MS associated variants are >90% non-coding but may impact gene expression and/or alternative splicing. We hypothesise that single-cell transcriptomics provides greater mechanistic insights into how MS associated variants affect gene expression or splicing across individual cells. The aim is to use innovative approaches to investigate this hypothesis. Understanding the mechanism of action of MS associated variants is a key challenge with important translational implications towards improved treatments and personalised medicine.