Genetics of Multiple Sclerosis

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system with a global median prevalence of 33 per 100,000 habitants. The etiology of the disease is not entirely understood, but it is becoming evident that interplay between environmental and genetic factors is necessary to trigger the disease. An important effort has been made to determine the risk loci of MS. From the determination of associated variants in the major histocompatibility complex (MHC) in 1972 to the actual knowledge of 200 loci that independently contribute to the disease it has come a long way. The genome-wide association studies (GWASs) in MS in large populations in combination with expression quantitative loci (eQTL) and a better understanding of the functional elements in the human genome have promoted a deeper knowledge of MS genetics in the last 10 years. However, we are still far from understanding the genetic implication in the disease. The determination of the “missing heritability,” the genetic factors that lead to the heterogeneity of the disease, the functional effects of the associated variants, and the definition of the pathways altered in MS are the actual focus of attention of the MS genetic studies.