An approximate Bayesian significance test for genomic evaluations

Biom J. 2018 Nov;60(6):1096-1109. doi: 10.1002/bimj.201700219. Epub 2018 Aug 12.

Abstract

Genomic information can be used to study the genetic architecture of some trait. Not only the size of the genetic effect captured by molecular markers and their position on the genome but also the mode of inheritance, which might be additive or dominant, and the presence of interactions are interesting parameters. When searching for interacting loci, estimating the effect size and determining the significant marker pairs increases the computational burden in terms of speed and memory allocation dramatically. This study revisits a rapid Bayesian approach (fastbayes). As a novel contribution, a measure of evidence is derived to select markers with effect significantly different from zero. It is based on the credibility of the highest posterior density interval next to zero in a marginalized manner. This methodology is applied to simulated data resembling a dairy cattle population in order to verify the sensitivity of testing for a given range of type-I error levels. A real data application complements this study. Sensitivity and specificity of fastbayes were similar to a variational Bayesian method, and a further reduction of computing time could be achieved. More than 50% of the simulated causative variants were identified. The most complex model containing different kinds of genetic effects and their pairwise interactions yielded the best outcome over a range of type-I error levels. The validation study showed that fastbayes is a dual-purpose tool for genomic inferences - it is applicable to predict future outcome of not-yet phenotyped individuals with high precision as well as to estimate and test single-marker effects. Furthermore, it allows the estimation of billions of interaction effects.

Keywords: SNP; conditional expectation; dominance; epistasis; genetic architecture.

MeSH terms

  • Animals
  • Bayes Theorem
  • Biometry / methods*
  • Genomics*
  • Mice
  • Polymorphism, Single Nucleotide
  • Software