Exploring the genetic architecture of late-onset Alzheimer disease in an Amish population

Abstract

Late-onset Alzheimer disease (LOAD) is a complex neurodegenerative disorder with a strong genetic component. APOE is a well-established risk gene for LOAD, and several other genes have also been identified. However, at least half of the genetic component for LOAD remains unexplained. Genetic heterogeneity complicates identifying the remaining risk genes. To overcome this problem the objective of my thesis work was to study the Amish communities of Ohio and Indiana, a genetically isolated founder population to identify a novel LOAD risk gene(s). I first performed quality control procedures on a set of genome-wide single nucleotide polymorphisms (SNPs) genotyped in the Amish. I then performed genome-wide linkage and association analyses in the cleaned dataset. Lastly, I performed a candidate gene sequence analysis.