RT Journal Article
SR Electronic
T1 Variable prediction accuracy of polygenic scores within an ancestry group
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 629949
DO 10.1101/629949
A1 Hakhamanesh Mostafavi
A1 Arbel Harpak
A1 Dalton Conley
A1 Jonathan K Pritchard
A1 Molly Przeworski
YR 2019
UL http://biorxiv.org/content/early/2019/05/07/629949.abstract
AB 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.