Application of Bayesian genomic prediction methods to genome-wide association analyses

将贝叶斯基因组预测方法应用于全基因组关联分析

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Abstract

BACKGROUND: Bayesian genomic prediction methods were developed to simultaneously fit all genotyped markers to a set of available phenotypes for prediction of breeding values for quantitative traits, allowing for differences in the genetic architecture (distribution of marker effects) of traits. These methods also provide a flexible and reliable framework for genome-wide association (GWA) studies. The objective here was to review developments in Bayesian hierarchical and variable selection models for GWA analyses. RESULTS: By fitting all genotyped markers simultaneously, Bayesian GWA methods implicitly account for population structure and the multiple-testing problem of classical single-marker GWA. Implemented using Markov chain Monte Carlo methods, Bayesian GWA methods allow for control of error rates using probabilities obtained from posterior distributions. Power of GWA studies using Bayesian methods can be enhanced by using informative priors based on previous association studies, gene expression analyses, or functional annotation information. Applied to multiple traits, Bayesian GWA analyses can give insight into pleiotropic effects by multi-trait, structural equation, or graphical models. Bayesian methods can also be used to combine genomic, transcriptomic, proteomic, and other -omics data to infer causal genotype to phenotype relationships and to suggest external interventions that can improve performance. CONCLUSIONS: Bayesian hierarchical and variable selection methods provide a unified and powerful framework for genomic prediction, GWA, integration of prior information, and integration of information from other -omics platforms to identify causal mutations for complex quantitative traits.

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