Multiple sclerosis (MS) is a complex genetic disease. In addition to a modest heritability of risk, multifaceted gene-environment interactions play a role in causing disease. Although the exact mechanisms involved in MS pathogenesis remain unclear, both genetic and environmental factors have been implicated in susceptibility. It seems likely that both heritable and environmental factors also contribute to determine the clinical course of the disease. The challenge for MS research is to identify the primary genetic and environmental etiologic factors and to find ways to minimize their impact. Given the complexities involved, unraveling the relationships between these factors is extremely difficult and to date has had limited success.
A role for heritability was suggested in the early descriptions of MS, even before the advent of modern genetics. Epidemiologic studies have provided us with a number of critical insights, including our awareness that the condition may be familial (1896), our appreciation of differences in gender-related and ethnic risks (1921), our understanding of the recurrence risk in families, and our description of the major histocompatibility complex class I and II associations. The evidence for the role of environmental factors in MS pathogenesis includes a higher prevalence of disease at higher latitudes, the apparent presence of clusters in some areas, and the absence of complete penetrance, even in monozygotic twins. The precise nature of the interplay between genetic and environmental factors is unknown.