Variable prediction accuracy of polygenic scores within an ancestry group

Fields as diverse as human genetics and sociology are increasingly using
polygenic scores based on genome-wide association studies (GWAS) for
phenotypic prediction. However, recent work has shown that polygenic
scores have limited portability across groups of different genetic
ancestries, restricting the contexts in which they can be used reliably
and potentially creating serious inequities in future clinical
applications. Using the UK Biobank data, we demonstrate that even within a
single ancestry group (i.e., when there are negligible differences in
linkage disequilibrium or in causal alleles frequencies), the prediction
accuracy of polygenic scores can depend on characteristics such as the
socio-economic status, age or sex of the individuals in which the GWAS and
the prediction were conducted, as well as on the GWAS design. Our findings
highlight both the complexities of interpreting polygenic scores and
underappreciated obstacles to their broad use.