The role of vitamin D and of sun exposure is another area of related epidemiologic research. Some data suggest that the risk of MS is in part a result of a lack of exposure to these two related environmental features (Munger et al; van der Mei et al). Whether this partly explains the latitudinally graded risk is unclear. An observed seasonal fluctuation in the activity of established MS lesions may have a similar basis.
Several studies indicate that persons who migrate from a high-risk to a low-risk zone carry with them at least part of the risk of their country of origin and genetic makeup, even though the disease may not become apparent until 20 years after migration. Such a pattern has been demonstrated in both South Africa and Israel. Dean determined that the prevalence of MS in native-born white South Africans was 3 to 11 per 100,000, whereas the rate in immigrants from northern Europe was approximately 50 per 100,000, only slightly less than among the nonimmigrating natives of those countries. The data of Dean and Kurtzke indicate further that in persons who had immigrated before the age of 15, the risk was similar to that of native-born South Africans; whereas in persons who had immigrated after that age, the risk was similar to that of their birthplace. Alter and colleagues found that in the descendants of European immigrants born in Israel, the risk of MS was low, similar to that of other native-born Israelis, whereas among recent immigrants the incidence in each national group approached that of the land of birth. Again, the critical age of immigration appeared to be about 15 years. These older epidemiologic studies and others have suggested that MS is associated with particular localities rather than with a particular ethnic group in those localities, and implicate environmental factors but not to the exclusion of genetic susceptibility. However, more current studies suggest the opposite; that genetic factors in a population predominate.
A familial aggregation of MS is now well established. Approximately 15 percent of MS patients have an affected relative, with the highest risk of concurrence being observed in the patient’s siblings (Ebers, 1983). In a large population-based study carried out in British Columbia by Sadovnick and colleagues (1988), it was found that almost 20 percent of index cases had an affected relative, again with the highest risk in siblings. In a subsequent study, Sadovnick and colleagues (1996) sought to determine the degree of heritability of MS by comparing the risk of disease in the half-sibs (1 biologic parent in common) of affected individuals with the risk in full sibs; the risk for full sibs was 2 to 3 times greater than for half-sibs and they interpreted these results as clearly genetic in basis.
The case for heritability is further supported by studies of twins in whom one of each pair is known to have MS. In the most extensive of these studies (Ebers et al), the diagnosis was verified in 12 of 35 pairs of monozygotic twins (34 percent) and in only 2 of 49 pairs of dizygotic twins (4 percent). Furthermore, in 2 additional sets of monozygotic twins who were clinically normal, lesions were detected by MRI. The concordance rate in dizygotic pairs is similar to that in nontwin siblings. Despite these provocative findings, no consistent pattern of mendelian inheritance has emerged. Of course, one must not assume that all diseases with an increased familial incidence are hereditary in that instances of the same condition in several members of a family may simply reflect an exposure to a common environmental agent. Paralytic poliomyelitis, for example, was about 8 times more common in immediate family members than in the population at large.