Although our simulation study provides important insight into the future of PRS use, it has important limitations. First, while coalescent simulations allow for decreased computational burden, model assumptions may result in inaccurate long-range LD, especially for whole-genome simulations.30 However, given we only simulated chromosome 20, biases are expected to be modest.30 We also use a case-control framework for our simulation; therefore, power and potential differences in population PRS accuracy may be even higher if a quantitative trait was used. In addition, our simulations assume random mating among admixed individuals and therefore do not reflect the more complex assortative mating that may be observed, which may impact the distribution of local ancestry tract lengths in our simulation and therefore hinder the improvement of PRS accuracy by local ancestry weighting.31 Also, although we provide evidence to suggest the contribution of population differences in allele frequency and LD tagging of causal variants to loss of PRS accuracy with varying ancestry, we do not delineate how each of these factors decreases accuracy independently; this is a direction for future work. Finally, we have only
