Polygenic prediction via Bayesian regression and continuous shrinkage priors

Nat Commun. 2019 Apr 16;10(1):1776. doi: 10.1038/s41467-019-09718-5.


Polygenic risk scores (PRS) have shown promise in predicting human complex traits and diseases. Here, we present PRS-CS, a polygenic prediction method that infers posterior effect sizes of single nucleotide polymorphisms (SNPs) using genome-wide association summary statistics and an external linkage disequilibrium (LD) reference panel. PRS-CS utilizes a high-dimensional Bayesian regression framework, and is distinct from previous work by placing a continuous shrinkage (CS) prior on SNP effect sizes, which is robust to varying genetic architectures, provides substantial computational advantages, and enables multivariate modeling of local LD patterns. Simulation studies using data from the UK Biobank show that PRS-CS outperforms existing methods across a wide range of genetic architectures, especially when the training sample size is large. We apply PRS-CS to predict six common complex diseases and six quantitative traits in the Partners HealthCare Biobank, and further demonstrate the improvement of PRS-CS in prediction accuracy over alternative methods.

Publication types

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

MeSH terms

  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / genetics
  • Bayes Theorem
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Computer Simulation
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / genetics
  • Databases, Genetic / statistics & numerical data
  • Depression / diagnosis
  • Depression / genetics
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / genetics
  • Linkage Disequilibrium / genetics
  • Male
  • Models, Genetic*
  • Multifactorial Inheritance / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait, Heritable*
  • Risk Factors