SummaryAUC: a tool for evaluating the performance of polygenic risk prediction models in validation datasets with only summary level statistics

Abstract

MotivationPolygenic risk score (PRS) methods based on genome-wide association studies (GWAS) have a potential for predicting the risk of developing complex diseases and are expected to become more accurate with larger training data sets and innovative statistical methods. The area under the ROC curve (AUC) is often used to evaluate the performance of PRSs, which requires individual genotypic and phenotypic data in an independent GWAS validation dataset. We are motivated to develop methods for approximating AUC of PRSs based on the summary level data of the validation dataset, which will greatly facilitate the development of PRS models for complex diseases.ResultsWe develop statistical methods and an R package SummaryAUC for approximating the AUC and its variance of a PRS when only the summary level data of the validation dataset are available. SummaryAUC can be applied to PRSs with SNPs either genotyped or imputed in the validation dataset. We examined the performance of SummaryAUC using a large-scale GWAS of schizophrenia. SummaryAUC provides accurate approximations to AUCs and their variances. The bias of AUC is typically less than 0.5% in most analyses. SummaryAUC cannot be applied to PRSs that use all SNPs in the genome because it is computationally prohibitive.Availabilityhttps://github.com/lsncibb/SummaryAUCContactJianxin.Shi@nih.gov

Polygenic risk scores: effect estimation and model optimization

“…Even if such a dataset is available, researchers may prefer to use it as the testing dataset to report the optimized PRS's predictive performance, rather than holding it out as a validation dataset for model selection. To address this challenge, Summar-yAUC is a new approach designed for assessing PRS's prediction accuracy using summary-level data as the validation set [23]. For a case-control GWAS, Summar-yAUC estimates the area under the ROC curve (AUC) by calculating the probability that a randomly selected case has a higher PRS than a randomly selected control.…”