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, the prediction accuracy of polygenic scores depends on characteristics such as the age or sex composition of the individuals in which the GWAS and the prediction were conducted, and on the GWAS study design. Our findings highlight both the complexities of interpreting polygenic scores and underappreciated obstacles to their broad use.
For my podcast, I recently talked to the first author of Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. He turned out to be pretty sanguine about this result. We’re in the early years of the polygenic risk scores. There’s going to be a lot to learn…