Because they rely on LD patterns, which vary ancestrally, PRS derived from a discovery GWAS of Europeans might not be an informative predictor in another ancestral group. Even within ancestral groups, inclusion of indices of nuanced ancestral variability derived from GWAS data, can significantly improve prediction in PRS analyses by eliminating such spurious admixture effects from the weighted PRS (Chen et al., 2015). Studies have begun to probe whether PRS generated from one ancestral population may be predictive of the same phenotype in another. For example, Bigdeli and colleagues (Bigdeli et al., 2017) combined results from the aforementioned CONVERGE Han Chinese cohort with those from a large GWAS meta-analysis of Europeans to report a trans-ancestry genetic correlation of ~0.30 – 0.40. However, LDpred PRS-based analyses were only predictive of recurrent depression, but not other depression phenotypes, after correction for multiple testing (R2=0.002). A similar study found that PRS derived from a GWAS of neuroticism in 170,910 individuals participating in the European UK Biobank (Okbay et al., 2016) predicted variance in both depression (R2=0.001) and neuroticism (R2=0.083) in Han Chinese women
