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Chunk #35 — METHODS — Alternative PRS construction methods — PT:

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Improving polygenic prediction in ancestrally diverse populations.
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LD-informed pruning and p-value thresholding (PT)35 selects clumped SNPs of a certain statistical significance to be included in the PRS calculation. We performed PT using PRSice-244 with the default parameter settings: the clumping was performed with a radius of 250kb and an r2 threshold of 0.1. We used 1KG super-population samples (EUR, EAS, AFR or AMR) whose ancestry matched the discovery sample as the LD reference panel for clumping. The p-value threshold among 10−8, 10−7, 10−6, 10−5, 3×10−5, 10−4, 3×10−4, 0.001, 0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 that maximized the R2 in the validation dataset was selected, and used in the independent testing dataset to calculate the final PRS and its performance metrics.