title: Exploring the predictive power of polygenic scores derived from genome-wide association studies: a study of 10 complex traits.
abstract: It is hoped that advances in our knowledge in disease genomics will contribute to personalized medicine such as individualized preventive strategies or early diagnoses of diseases. With the growth of genome-wide association studies (GWAS) in the past decade, how far have we reached this goal? In this study we explored the predictive ability of polygenic risk scores (PRSs) derived from GWAS for a range of complex disease and traits.
  
  
  
  We first proposed a new approach to evaluate predictive performances of PRS at arbitrary P -value thresholds. The method was based on corrected estimates of effect sizes, accounting for possible false positives and selection bias. This approach requires no distributional assumptions and only requires summary statistics as input. The validity of the approach was verified in simulations. We explored the predictive power of PRS for ten complex traits, including type 2 diabetes (DM), coronary artery disease (CAD), triglycerides, high- and low-density lipoprotein, total cholesterol, schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder and anxiety disorders. We found that the predictive ability of PRS for CAD and DM were modest (best AUC = 0.608 and 0.607) while for lipid traits the prediction R-squared ranged from 16.1 to 29.8%. For psychiatric disorders, the predictive power for SCZ was estimated to be the highest (best AUC 0.820), followed by BD. Predictive performance of other psychiatric disorders ranged from 0.543 to 0.585. Psychiatric traits tend to have more gradual rise in AUC when significance thresholds increase and achieve the best predictive power at higher P -values than cardiometabolic traits.
  
  
  
  hcso@cuhk.edu.hk ; pcsham@hku.hk.
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.|KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Zoology Institute of Zoology and Chinese University of Hong Kong, Hong Kong.
authors.forename: Hon-Cheong
authors.initials: HC
authors.lastname: So
authors.affiliation: Department of Psychiatry, University of Hong Kong, PokFuLam, Hong Kong.|Centre for Genomic Sciences, University of Hong Kong, PokFuLam, Hong Kong.|State Key Laboratory for Cognitive and Brain Sciences, University of Hong Kong, PokFuLam, Hong Kong.|Centre for Reproduction, Development and Growth, University of Hong Kong, PokFuLam, Hong Kong.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
mesh_terms: D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics