TITLE: “Large uncertainty in individual PRS estimation impacts PRS-based risk stratification.”
ABSTRACT: Large-scale genome-wide association studies have enabled polygenic risk scores (PRS), which estimate the genetic value of an individual for a given trait. Since PRS accuracy is typically assessed using cohort-level metrics, uncertainty in PRS estimates at individual level remains underexplored. In this talk, we will first introduce a Bayesian framework that can estimate the variance of an individual’s PRS and can yield well-calibrated credible intervals for the genetic value of a single individual. Then we will discuss the impact of PRS uncertainty on risk stratification and present a probabilistic PRS-based risk stratification approach to incorporate the uncertainty in individual PRS estimates. Finally, we’ll present a theoretical estimate of individual PRS variance as a function of heritability, number of causal SNPs and sample size.
