Amyotrophic lateral sclerosis (ALS) is a rare condition that is thought to occur as a result of an interaction between genetic risk and environmental exposures. Although a number of major genes are known to cause ALS in up to 15% of patients with a familial form of the disease, the precise genetic factors that increase risk in the remainin 85% o are not well understood. Similarly, the environmental factors that increase risk have not been well established. The availability of population-based disease registers have allowed us to accurately calculate the incidence of ALS in populations of European ancestral origin. These registers have also allowed us to conduct large studies of cases and controls to increase our understanding of environmental risk factors, and to begin to understand gene-environment interactions that might increase this risk of developing ALS. Conversely, little is known about the true rates or characteristics of the condition in populations outside of Europe and the United States, and in those of mixed ancestral origin. There is some evidence to suggest that the rates of ALS are lower in the Hispanic population in North America, but this may be due to difficulties encountered by minorities in accessing healthcare. Because ALS is rare large scale population based studies of incidence, prevalence, phenotype and risk factors are necessary. Detailed population based studies including all minority groups are challenging to perform in the United States, notwithstanding the recent development of the CDC ALS Registry. Moreover, the ALS Registry does not have the facility to capture incident cases in real time. We have already undertaken a large population based incident study in Europe as part of a Research Consortium (The European multidisciplinary ALS network identification to cure motor neurone degeneration, EuroMOTOR). To understand the impact of ancestral origin and geographic exposure on ALS in the United States, we now propose to use the methods developed by our EuroMOTOR Consortium study ALS in 3 populations from South America that are of mixed ancestral origin. The purpose of this study is to compare the rates and features of ALS in Hispanic populations with the rates and features of ALS in European populations. We will also use our established methods to collect information about occupational history and various exposures to determine whether the risks in Hispanic patients from South America are similar to those we identify in European populations. The outcome of this work will establish for the first time whether Hispanic populations in the Americas have lower rates of ALS compared to Europeans, whether the features of the disease are the same, and whether the risks of developing the disease differ depending on geographic and ancestral origin. This will help to understand the variance in ALS rates across the United States, and will help to test the hypothesis that Hispanic populations in the United States are protected from developing the disease. This in turn will help us to develop new models of disease causation in the United States ALS population, that can in turn help us to find new therapies for all forms of ALS.