Genetic studies of multiple sclerosis and neuromyelitis optica: Current status in European, African American and Asian populations

Multiple sclerosis (MS) pathogenesis results from both genetic and environmental factors. Genome-wide association studies (GWAS) have contributed considerably to our understanding of MS susceptibility through identification of genetic variants influencing risk and quantitation of their effect sizes. Immunologically relevant genes, including genes in the major histocompatibility complex region, are the primary genetic contributors to MS susceptibility. MS prevalence differs according to population, and most GWAS carried out to date have used datasets from people of European descent. Interpretation and application of GWAS results from Europeans to other populations require a good understanding of the genetic characteristics of each population, such as linkage disequilibrium patterns. The heterogeneity in global MS prevalence is partially explained by differences in risk allele frequencies in populations, which are due to the effects of migration, adaptation to new environments and genetic heterogeneity. Genetic studies of different populations can be expected to narrow down the putative causative regions and improve our understanding of MS pathogenesis. The literature record of genetic studies of neuromyelitis optica is much shorter than that of MS. Genes associated with neuromyelitis optica have been reported in the major histocompatibility complex region, as well as at other genetic loci, but only the susceptibility associated with the HLA-DPB1*05:01 and HLA-DRB1*03 alleles, and the association of a CYP7A single nucleotide polymorphism have been replicated. Here, we describe important genetic studies of MS and neuromyelitis optica in Europeans, African Americans, and Asians, and discuss the implications for disease incidence and future directions for genetic research.