Low transferability of height polygenic risk scores in admixed ancestry populations

Abstract Polygenic risk scores (PRS) summarize the results of GWAS into a single number that can predict quantitative phenotype or disease risk. One barrier to the use of PRS in clinical practice is that the majority of GWAS come from cohorts of European ancestry, and predictive power is lower in non-European ancestry cohorts. There are many possible reasons for this decrease; here we show that differences in allele frequencies, LD patterns, and phenotypic variance across ancestries are unlikely to be driving this pattern.

Polygenic risk scores perform poorly across populations

Abstract | The vast majority of genome-wide association studies (GWAS) are performed in cohorts of European ancestry. Systematic differences in polygenic risk scores (PRS) between European and non-European ancestry populations are believed to be largely spurious. However, it is not clear whether they are completely inaccurate nor how much individual-level predictive power is lost by applying PRS based on European-ancestry GWAS to non-European ancestry populations. Finally, a quantitative understanding of the biological or statistical basis for the poor performance of PRS in non-European-ancestry populations is lacking.