Significant Sparse Polygenic Risk Scores across 428 traits in UK Biobank

We present a systematic assessment of polygenic risk score (PRS) prediction across more than 1,600 traits using genetic and phenotype data in the UK Biobank. We report 428 sparse PRS models with significant (p < 2.5 x 10-5) incremental predictive performance when compared against the covariate-only model that considers age, sex, and the genotype principal components. We report a significant correlation between the number of genetic variants selected in the sparse PRS model and the incremental predictive performance in quantitative traits (Spearmans {rho} = 0.54, p = 1.4 x 10-15), but not in binary traits ({rho} = 0.059, p = 0.35). The sparse PRS model trained on European individuals showed limited transferability when evaluated on individuals from non-European individuals in the UK Biobank. We provide the PRS model weights on the Global Biobank Engine (https://biobankengine.stanford.edu/prs).