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CalPred yields calibrated intervals for polygenic risk prediction

Shi, Z.; Zhang, Z.; Mandla, R.; Hou, K.; Pasaniuc, B.

2026-04-22 genetic and genomic medicine
10.64898/2026.04.21.26351410 medRxiv
Show abstract

Polygenic scores (PGS) have emerged as a useful biomarker for stratification of high-risk individuals in genomic medicine, with prediction intervals arising as a principled approach to incorporate statistical uncertainty in their individual-level predictions. In contrast to recent reports by Xu et al7, we show that CalPred6 provides well-calibrated prediction intervals that contain the trait phenotypes at targeted confidence levels. CalPred maintains calibration when PGS performance varies across contextual factors (e.g., ancestry, age, sex, or socio-economic factors) whereas PredInterval7 - a recently introduced method that focuses on marginal calibration across all individuals - exhibits miscalibration.

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