A multiple-phenotype imputation method for genetic studies

Nat Genet. 2016 Apr;48(4):466-72. doi: 10.1038/ng.3513. Epub 2016 Feb 22.

Abstract

Genetic association studies have yielded a wealth of biological discoveries. However, these studies have mostly analyzed one trait and one SNP at a time, thus failing to capture the underlying complexity of the data sets. Joint genotype-phenotype analyses of complex, high-dimensional data sets represent an important way to move beyond simple genome-wide association studies (GWAS) with great potential. The move to high-dimensional phenotypes will raise many new statistical problems. Here we address the central issue of missing phenotypes in studies with any level of relatedness between samples. We propose a multiple-phenotype mixed model and use a computationally efficient variational Bayesian algorithm to fit the model. On a variety of simulated and real data sets from a range of organisms and trait types, we show that our method outperforms existing state-of-the-art methods from the statistics and machine learning literature and can boost signals of association.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Animals, Outbred Strains
  • Bayes Theorem
  • Blood Platelets / physiology
  • Chickens
  • Female
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Models, Genetic
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Rats
  • T-Lymphocytes / physiology
  • Triticum / genetics