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

Lars G Fritsche; Snehal Patil; Lauren J Beesley; Peter VandeHaar; Maxwell Salvatore; Ying Ma; Robert B Peng; Daniel Taliun; Xiang Zhou; Bhramar Mukherjee

doi:10.1016/j.ajhg.2020.08.025

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.

Authors

Affiliations

¹ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Precision Health Data Science, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: larsf@umich.edu.
² Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
³ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Precision Health Data Science, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
⁴ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Precision Health Data Science, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Department of Statistics, Northwestern University, Evanston, IL 60208, USA.
⁵ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Precision Health Data Science, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
⁶ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Center for Precision Health Data Science, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Michigan Institute for Data Science, University of Michigan, Ann Arbor, MI 48109, USA; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: bhramar@umich.edu.

Abstract

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

Abstract

Publication types

MeSH terms

Grants and funding