Polygenic risk scores: effect estimation and model optimization

Abstract

Background: Polygenic risk score (PRS) derived from summary statistics of genome-wide association studies (GWAS) is a useful tool to infer an individual’s genetic risk for health outcomes and has gained increasing popularity in human genetics research. PRS in its simplest form enjoys both computational efficiency and easy accessibility, yet the predictive performance of PRS remains moderate for diseases and traits.

Results: We provide an overview of recent advances in statistical methods to improve PRS’s performance by incorporating information from linkage disequilibrium, functional annotation, and pleiotropy. We also introduce model validation methods that fine-tune PRS using GWAS summary statistics.

Conclusion: In this review, we showcase methodological advances and current limitations of PRS, and discuss several emerging issues in risk prediction research.

Graphical abstract

Keywords

GWAS / polygenic risk score / summary statistics / model selection

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