In addition to genotypes of simulated admixed individuals, RFMIX13 also outputs the local ancestry at each locus for every individual. Thus, we used this information to create a local ancestry weighted PRS that is not impacted by ancestry inference errors. For admixed African and European ancestry individuals, an ancestry-specific PRS was constructed for each population (k) by limiting each PRS to variants found in that ancestry-specific subset of the genome (i∈k), as defined by local ancestry, and weighting using variant effects discovered in that population.7 Each ancestry-specific PRS was then combined, weighted by the genome-wide global ancestry proportion (ρk) for that individual as follows:7PRS=ρEUR∑i∈EURβi,EURgi+1−ρEUR∑i∈AFRβi,AFRgiIn this way, each individual has a PRS constructed from the same independent variants with personalized weights that are unique to the individual’s local ancestry.
