Evaluating the Role of Race, Ethnicity, and Genetic Ancestry in Alzheimer Disease-associated Genes
MentorMargaret A. Pericak-Vance, PhD John P. Hussman Institute for Human Genomics at Miller School of Medicine, University of Miami
The strongest risk gene identified for Alzheimer disease (AD) is APOE. However, this gene does not increase the risk for AD in every ethnic population. For example, individuals with an African ethnic background do not seem to be very affected by this variation. This is due to the fact that individuals from different races/ethnicities harbor genetic differences at the site of the APOE gene. This is why it is important to study populations separately and to take into account their genetic background, also called local ancestry, when analyzing the genetic effect on the disease. We propose to explore the relationship between local ancestry of African-American and Caribbean-Hispanic people and AD risk genes. We will facilitate the discovery of ethnic-specific genes and genetic changes increasing the risk for AD. This approach will allow us to move a further step toward personalized and precision medicine.
Our goal in this study is to evaluate the role of race/ethnicity and ancestry-specific genetic factors in known Alzheimer disease (AD) genes in our multi-ethnic dataset, and to identify novel risk loci correlated with genetic ancestry. In the experimental design, we will perform a series of ancestry-aware statistical tests to characterize the influence of ancestral background located in or near the genomic region of known genes in AD. Furthermore, to identify novel genes specifically through under-studied ancestries, such as African and Amerindian ancestral backgrounds, we will perform genome-wide analysis by testing the genetic factors in the context of genetic ancestry. This study will be the first study to systematically assess the role of genetic ancestry on AD risk in a diverse set of multi-ethnic samples, potentially leading to a set of genes and genomic regions that modify existing AD risk factors. This gives us the opportunity to identify novel factors influencing AD that may contribute to health disparities. New test approach will provide insights about the risk factors correlated with ancestral backgrounds and will enhance the power and extend studies in under-studied populations. In particular, identification of population-specific variations that influence disease could inform precision medicine initiatives, and lead to development of ancestry-specific AD treatments. This would improve treatments, and help reduce health disparities.