Genetic and Environmental Risk Factors in Multiple Sclerosis Multiplex Families

Multiple sclerosis (MS) is a complex neurological disease that clusters in families. In fact, 20% of MS patients have an affected family member. In addition, first-degree family members are at a higher risk of developing MS compared to general population. Etiology of MS includes both genetic and environmental factors. The strongest and most studied genetic risk factor of MS susceptibility is the HLA-DRB1*1501 allele. For several decades, HLA-class II region was the only known genetic risk factor for MS. With the improvement of technology and application of genome-wide association studies, more than 200 other risk loci were discovered. Despite discovery of genetic and several other biomarkers, MS heritability is not completely explained and prediction of MS in apparently healthy family members is still very limited. The studies described in this thesis are executed in a unique collection of Dutch MS patients and their family members who belong to the MS multiplex families. Our aim was to explore genetic (known and unknown) and environmental factors in MS patients and their family members, and to study how these factors relate to MS risk in the family members. In addition, we studied how risk genes of adult MS patients can be compared to risk genes in children with MS.