Multiple sclerosis - How common variants influence disease phenotype and rare variants trigger onset of disease

Multiple sclerosis (MS) is a common neuroinflammatory disorder that is characterized by inflammation, demyelination and axonal loss. Epidemiological studies have shown the importance of both genetic and environmental factors in the development of the disease. Large-scale screens in international study populations, of which the Belgian cohort was a part, have identified four classical HLA and 110 non-HLA susceptibility loci. These variants are common in the general population and, with the exception of the HLA region (e.g. HLADRB1*15:01: odds ratio (OR) = 3.1), individually exert modest effects (OR = 1.03–1.34). During my PhD, I will elaborate on previous efforts by calculating MS risk based on the current extended list of MS risk variants and investigate the effect on MS phenotype. Despite the success of GWAS, the currently known genetic risk variants explain only 27% of the variance in MS risk. Therefore, a second question that I will address in my PhD is which additional inherited and non-inherited genetic factors determine whether or not an individual will develop MS.