BridgePRS leverages shared genetic effects across ancestries to increase polygenic risk score portability

Abstract Here we present BridgePRS, a novel Bayesian polygenic risk score (PRS) method that leverages shared genetic effects across ancestries to increase PRS portability. We evaluate BridgePRS via simulations and real UK Biobank data across 19 traits in individuals of African, South Asian and East Asian ancestry, using both UK Biobank and Biobank Japan genome-wide association study summary statistics; out-of-cohort validation is performed in the Mount Sinai (New York) Bio Me biobank. BridgePRS is compared with the leading alternative, PRS-CSx, and two other PRS methods. Simulations suggest that the performance of BridgePRS relative to PRS-CSx increases as uncertainty increases: with lower trait heritability, higher polygenicity and greater between-population genetic diversity; and when causal variants are not present in the data. In real data, BridgePRS has a 61% larger average R 2 than PRS-CSx in out-of-cohort prediction of African ancestry samples in Bio Me ( P  = 6 × 10 −5 ). BridgePRS is a computationally efficient, user-friendly and powerful approach for PRS analyses in non-European ancestries.