Multiple sclerosis genetics

Familial aggregation and the studies of twins indicate that heredity contributes to multiple sclerosis (MS) risk. Immunologic studies of leukocyte antigens subsequently followed by gene-mapping techniques identified the primary MS susceptibility locus to be within the major histocompatibility complex (MHC). The primary risk allele is HLA-DRB1*15, although other alleles of this gene also influence MS susceptibility. Other genes within the MHC also contribute to MS susceptibility. Genome-wide association studies have identified over 50 additional common variants of genes across the genome. Estimates suggest that there may be as many as 200 genes involved in MS susceptibility. In addition to these common polymorphisms, studies have identified several rare risk alleles in some families. Interestingly, the majority of the genes identified have known immunologic functions and many contribute to the risk of inheriting other autoimmune diseases. Genetic variants in the vitamin D metabolic pathway have also been identified. That vitamin D contributes to MS susceptibility as both an environmental as well as genetic risk factor underscores the importance of this metabolic pathway in disease pathogenesis. Current efforts are focused on understanding how the myriad of genetic risk alleles interact within networks to influence MS risk at family level as well as within populations.