PRS Center for Admixed Populations

Polygenic risk scores (PRS), that aggregate risk across common variants in the genome, have emerged as a powerful tool towards implementing genomic medicine. Unfortunately, the vast majority of genomic data from which current PRS are estimated is coming only from European ancestry individuals thus prohibiting the implementation of PRS for all individuals across the United States (US) and beyond. Of particular interest are individuals with recent ancestry from multiple continental sources whose genomes are a mosaic of segments of various ancestries. Such a range in genetic ancestry raises unique challenges in PRS method development as the accuracy of existing PRS varies across genomic ancestries. Unlike existing paradigm that largely views genetic ancestry as a confounder in PRS studies, we aim to fully integrate population genetics of the admixture process to yield admixture-PRS that provide improved accuracies for all individuals irrespective of genetic ancestries. We will integrate data of over 230,000 admixed individuals across five medical systems including UCLA, Mt Sinai, Colorado to develop, calibrate and benchmark PRS for admixed individuals.