Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations

• DOI: 10.1038/s41467-020-17719-y
• Publication Date: 2020-07-31T10:05:51Z
• Authors: Ying Wang; Jing Guo; Guiyan Ni; Jian Yang; Peter M. Visscher; Loic Yengo
• Keywords: Genome-wide Association Study; Linkage Disequilibrium; Genetic Association; Minor allele frequency; SNP; Multifactorial Inheritance

Abstract Polygenic scores (PGS) have been widely used to predict disease risk using variants identified from genome-wide association studies (GWAS). To date, most GWAS conducted in populations of European ancestry, which limits the use GWAS-derived PGS non-European ancestry populations. Here, we derive a theoretical model relative accuracy (RA) across ancestries. We show through extensive simulations that RA based on significant SNPs can be predicted accurately modelling linkage disequilibrium (LD), minor allele frequencies (MAF), cross-population correlations causal SNP effects and heritability. find LD MAF differences between ancestries explain 70 80% loss European-based African for traits like body mass index type 2 diabetes. Our results suggest underlying common genetic variation are mostly shared continents.