Cancer PRSweb: An Online Repository with Polygenic Risk Scores for Major Cancer Traits and Their Evaluation in Two Independent Biobanks

Am J Hum Genet. 2020 Nov 5;107(5):815-836. doi: 10.1016/j.ajhg.2020.08.025. Epub 2020 Sep 28.


To facilitate scientific collaboration on polygenic risk scores (PRSs) research, we created an extensive PRS online repository for 35 common cancer traits integrating freely available genome-wide association studies (GWASs) summary statistics from three sources: published GWASs, the NHGRI-EBI GWAS Catalog, and UK Biobank-based GWASs. Our framework condenses these summary statistics into PRSs using various approaches such as linkage disequilibrium pruning/p value thresholding (fixed or data-adaptively optimized thresholds) and penalized, genome-wide effect size weighting. We evaluated the PRSs in two biobanks: the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort at Michigan Medicine, and the population-based UK Biobank (UKB). For each PRS construct, we provide measures on predictive performance and discrimination. Besides PRS evaluation, the Cancer-PRSweb platform features construct downloads and phenome-wide PRS association study results (PRS-PheWAS) for predictive PRSs. We expect this integrated platform to accelerate PRS-related cancer research.

Keywords: EHR; GWAS; PRS; PheWAS; cancer genetics; complex traits; electronic health records; genome-wide association studies; phenome-wide association studies; polygenic risk scores.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biological Specimen Banks / statistics & numerical data*
  • Female
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Genome-Wide Association Study
  • Genomics / methods*
  • Humans
  • Internet
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Multifactorial Inheritance*
  • Neoplasms / classification
  • Neoplasms / diagnosis
  • Neoplasms / epidemiology
  • Neoplasms / genetics*
  • Phenotype
  • Quantitative Trait, Heritable
  • Risk Factors
  • United Kingdom / epidemiology
  • United States / epidemiology