There are several current limitations that restrict the broad utility and applicability of genetic risk prediction in research and clinical contexts, including insufficiently powered GWAS sample sizes for most complex traits, potential confounding in causal inference, and a lack of ancestral diversity in current studies. While the scale of GWAS has rapidly expanded over the last decade, most diseases still lack sufficient sample sizes for clinically relevant power from PRS (34). Furthermore, PRS comparing traits using GWAS for genetically uncorrelated phenotypes can lead to incorrect study conclusions from Type 1 error.
