Polygenic Risk Scores (PRS) have attracted increased attention in recent years as the power of PRS to predict individual disease risk has improved. These advances have been possible because of the development of tools for efficiently generating large genotype-phenotype datasets in European populations. Despite the remarkable advances in the development and application of PRS that have taken place, a significant limitation to their widespread use is the lack of tools and datasets that would allow application of PRS to Asian, African or Native American populations. In this talk I will focus on challenges to the development of PRS in Asian populations. South Asia in particular has a population whose genetics is the least characterized of any of the world’s major populations with a population structure that differs dramatically from that in Europe. I will describe studies that have characterized population structure in South Asia and tools that lay the foundations for economical and accurate genotyping at population-scale. Finally I will lay out the resource that will be built from these foundations and that will accelerate the development of PRS that are broadly applicable.