JointPRS: A Data-Adaptive Framework for Multi-Population Genetic Risk Prediction Incorporating Genetic Correlation

Genetic prediction accuracy for non-European populations is hindered by the limited sample size of Genome-wide association studies (GWAS) data in these populations. Additionally, it is challenging to tune model parameters with a small tuning dataset for methods that require tuning data, which is often the case for non-European samples. To address these challenges, we propose JointPRS, a novel, data-adaptive framework that simultaneously models multiple populations using GWAS summary statistics. JointPRS incorporates genetic correlation structures into the prediction framework, enabling accurate performance even without individual-level tuning data. Additionally, it uniquely employs a data-adaptive approach, providing a robust solution when only a small tuning dataset is available. Through extensive simulations and real data applications to 22 quantitative traits and four binary traits in five continental populations (European (EUR); East Asian (EAS); African (AFR); South Asian (SAS); and Admixed American (AMR)) evaluated using the UK Biobank (UKBB) and All of Us (AoU), we demonstrate that JointPRS outperforms six other state-of-art methods across three different data scenarios (no tuning data, tuning and testing data from the same cohort, and tuning and testing data from different cohorts) for most traits in non-European populations, while maintaining model simplicity and computational efficiency.