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Chunk #15 — RESULTS — Prediction of quantitative traits in Biobanks

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Improving polygenic prediction in ancestrally diverse populations.
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We next sought to replicate the relative performance of different PRS construction methods in the Taiwan Biobank (TWB)32, which is a community-based prospective cohort study of the Taiwanese population. Among the 33 quantitative traits we examined in UKBB and BBJ, 21 traits were also available in TWB. All PRS were trained on the UKBB and/or BBJ GWAS, validated in the UKBB EAS samples (where hyper-parameters were learnt; Supplementary Table 12), and evaluated in the TWB sample comprising 10,149 unrelated individuals, adjusting for age, sex and top 20 PCs of the genotypes. Figure 3b shows that single-discovery methods trained on UKBB and BBJ GWAS had similar performance in the TWB sample, even though UKBB GWAS were much larger (Fig. 3b; Supplementary Table 13). Bayesian multi-discovery methods showed substantial improvement in prediction accuracy compared with single-discovery methods. PRS-CSx provided a median improvement of 39.5% relative to PRS-CS (the best single-discovery method) and 8.2% relative to PRS-CS-mult (the second best multi-discovery method), suggesting the robustness of PRS-CSx when model parameters learnt in validation datasets were applied to external independent testing datasets. Overall, results in the TWB closely reproduced the patterns observed in the UKBB EAS samples (Fig. 3a, middle panel).