SESSION 9B Population Genetics and Epidemiology

It is generally stated that the incidence of ALS is the same throughout the world; however, there have been no wellconducted comparative studies of ALS occurrence among different populations, ethnic groups or defined geographic areas. Epidemiological studies in regions that comprise nonEuropeans have generally yielded lower figures. An ethnic difference in susceptibility to ALS has been invoked to explain the low rate of ALS in Mexico, but restricted access to medical care among lower socio-economic groups may also account for this finding. Similarly, small epidemiological studies in Rochester county, Minnesota, have reported variation in the presentation of ALS in different ethnic groups. More recently, Kasarskis et al. demonstrated a risk ratio for ALS of 0.61 in Blacks vs. Whites, and of 2.08 for Hispanics, Asians and Others vs. Whites, in a cohort drawn from veterans of the first Gulf war. Population-based epidemiological studies from Asia are limited. Mortality studies also suggest differences based on ethnicity. A study of mortality from ALS revealed lower rates among UK immigrants from the Indian subcontinent, the Caribbean, and Africa compared with the general population in England. More recent mortality data from the southern US also suggests a lower incidence of ALS in African-Americans. ALS is increasingly recognized as a complex genetic disease. Variations in phenotype have long been recognized, some of which correlate with specific Mendelian mediated genotypes (e.g. the autosomal recessive Scandinavian D90A mutation in SOD1). It is therefore likely that ethnic background may be important in determining the relationship between environmental risk factors and genetic susceptibility. The conflicting reports of the relative risks of various susceptibility genes including ApoE4, VEGF, SMN1 etc. may in part be due to population-based differences. Indeed, the carrier frequency of SMN1 differs considerably among different ethnic groups, as evidenced by a recent population-based study in Cuba. However, it does not always follow that genetic factors necessarily underlie variations in risk between ethnic groups. Studies in Guam have implicated both genetic and environmental factors that may underlie the high risk in this group. The definitive strategy for distinguishing genetic and environmental explanations for ethnic differences in disease risk is to study populations where there has been admixture between low-risk and high-risk groups. A population-based epidemiological study of ALS is ongoing in Cuba. The Cuban population is ethnically diverse and genetically admixed. Access to healthcare in Cuba is universal, and population-based epidemiology is feasible as a result. Using a panel of recently developed ethnicity specific polymorphic markers it will be possible to test the hypothesis that ALS occurs less frequently in populations of African ancestry than in those of European (mainly Spanish) ancestry. If the epidemiological observations are correct that ALS is less common in those of African descent, modern bioinformatics technology can be used to identify both ‘at risk’ and ‘protective’ genotypes that will help to elucidate disease pathogenesis.