ABSTRACT
It has long been recognized that, despite living at geographical latitudes where multiple sclerosis (MS) is common, genetically isolated ethnic groups-including Gypsies in Hungary (1); Indians and Orientals in North America (2); Aborigines in Australia (3); andMaoris in New Zealand (4)—remain resistant to the disease. Systematic analysis of familial aggregation of MS-in particular, studies of twins (5-8), adoptees (9), and half-siblings (10)—has also confirmed Eichhorst’s description from the 1890s of MS as a ‘‘heritable’’ disorder (11). The degree to which a disease is heritable can be estimated by dividing the lifetime risk of siblings to affected individuals by the population prevalence of the disease, to yield the so-called ks statistic. For MS, in high-risk populations, ks is between 20 (0.02/0.001) and 40 (0.04/0.001)—a value similar to that seen in insulin-dependent diabetes mellitus (12). Data from twin studies-which show that the concordance rate of approximately 30% in monozygotic twins drops steeply to a rate below 5% for dizygotic twins-strongly indicate that susceptibility to MS is influenced by many genes in combination (13).
