Genetic Of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic neurological disorder of CNS withpotentially devastating, long-term complications. The etiology of MS is stilluncertain, but the most updated working model for disease pathogenesisproposes the interplay between genetic and environmental factors asnecessary for MS manifestation. With the notable exception of the majorhistocompatibility complex (MHC), the identity of MS genetic determinantshas been elusive for decades. In recent years, the advent of genome-wideassociation studies (GWAS) and collaborative efforts among internationalcenters have fueled the characterization of several non-MHC loci associatedwith MS susceptibility. GWA studies have undoubtedly energized and changedthe field of MS genetics, allowing the discovery of more than a hundred riskloci following decades of unsuccessful attemptsConsidering the heterogeneity of MS and the intrinsic complexity of thehuman genome, a number of rational approaches can be envisioned tocharacterize the biological functions connected to MS susceptibility andpathophysiology.The goal of genetic studies is to achieve a more refined representation ofgenes, pathways, and networks involved in disease pathogenesis, and leveragethis information to discover novel targets for therapy, prevention, and repair.The next phase of the work will focus on identifying the causative variantsresponsible for association signals at every locus and defining their functionalroles, alone or in combinations, on the initiation and the clinical expression ofthe disease.