done in practice, but instead applied the same algorithm to each trait, based on two reference GWASs. While the first approach is useful for investigators who work with a single PRS and want to optimize it, it is also more case-dependent, and less generalizable. Our systematic approach is easier to apply on a number of traits and is appropriate for drawing general conclusions. Finally, we did not use multi-ethnic GWASs for PRS construction, but rather focused on EA and and Hispanic/Latino GWASs. Our goal was to more clearly delineate properties of the genetic architecture similarities or differences between populations. Another limitation of the current study is the lack of systematic investigation into generalizability of our results to other types of populations and varying sample sizes. It is a topic of future research as results from larger diverse studies become available. In the Supplementary Material, we report the results of a secondary analysis repeating the same data analysis reported in the manuscript, while evaluating PRSs on WHI African American women. Interestingly, the pattern of results is generally similar. This suggest that leveraging trans-ethnic information into PRS construction is beneficial.
