Genetic studies of diseases of aging have been done predominantly in clinic-based case-control datasets drawn from the general population. While these have the advantage of being relatively easy to collect and thus can generate large sample sizes, they do have limitations in ascertainment bias, differences in case and control ascertainment, and focus on genetic association analyses. Using special populations, such as the mid-Western Amish, overcomes several of these limitations. Over the past 15 years, we have worked collaboratively to collect phenotype and genotype information on the Amish of Holmes county in Ohio, and Elkhart, LaGrange, and Adams counties in Indiana. The Amish are culturally and genetically isolated and their lifestyle tends to be quite homogeneous, making genetic studies quite valuable. We have focused our efforts on two significant diseases of aging: Alzheimer disease (AD) and Age Related Macular Degeneration (AMD). Our ongoing studies have demonstrated that the genetic architecture of Ad and AMD differ significantly from the general population, strongly suggesting that novel loci exist in the Amish. Current studies are aimed at finding these novel loci using a combination of genome wide association and whole genome sequencing data.