Zhao Z, Yi Y, Song J, Wu Y, Zhong X, Lin Y, Hohman TJ, Fletcher J, Lu Q. PUMAS: fine-tuning polygenic risk scores with GWAS summary statistics. Genome biology. 2021 Dec 6;22(22). 257 p. PMID: 34488838 [PubMed] PMCID: PMC8419981
Polygenic risk scores (PRSs) have wide applications in human genetics research, but often include tuning parameters which are difficult to optimize in practice due to limited access to individual-level data. Here, we introduce PUMAS, a novel method to fine-tune PRS models using summary statistics from genome-wide association studies (GWASs). Through extensive simulations, external validations, and analysis of 65 traits, we demonstrate that PUMAS can perform various model-tuning procedures using GWAS summary statistics and effectively benchmark and optimize PRS models under diverse genetic architecture. Furthermore, we show that fine-tuned PRSs will significantly improve statistical power in downstream association analysis.