METHODS: PRS performance was evaluated using multivariable logistic regression and the area under the receiver operating characteristic curve (AUC).
RESULTS: Both European and Asian PRSs performed worse in H/L samples compared to original reports. The best European PRS performed better than the best Asian PRS in pooled H/L samples. European PRSs had decreased performance with increasing Indigenous American (IA) ancestry while Asian PRSs had increased performance with increasing IA ancestry. The addition of 2 H/L SNPs increased performance for all PRSs, most notably in the samples with high IA ancestry and did not impact the performance of PRSs in individuals with lower IA ancestry.
CONCLUSIONS: A single PRS that incorporates risk variants relevant to the multiple ancestral components of individuals from Latin America, instead of a set of ancestry specific panels, could be used in clinical practice.
IMPACT: Results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry specific variants into PRS for clinical application.