Locally epistatic models for genome-wide prediction and association by importance sampling

Deniz Akdemir, Jean-Luc Jannink, Julio Isidro-Sánchez

In statistical genetics, an important task involves building predictive models of the genotype-phenotype relationship to attribute a proportion of the total phenotypic variance to the variation in genotypes. Many models have been proposed to incorporate additive genetic effects into prediction or association models. Currently, there is a scarcity of models that can adequately account for gene by gene or other forms of genetic interactions, and there is an increased interest in using marker annotations in genome-wide prediction and association analyses. In this paper, we discuss a hybrid modeling method which combines parametric mixed modeling and non-parametric rule ensembles. This approach gives us a flexible class of models that can be used to capture additive, locally epistatic genetic effects, gene-by-background interactions and allows us to incorporate one or more annotations into the genomic selection or association models. We use benchmark datasets that cover a range of organisms and traits in addition to simulated datasets to illustrate the strengths of this approach. In this paper, we describe a new strategy for incorporating genetic interactions into genomic prediction and association models. This strategy results in accurate models, with sometimes significantly higher accuracies than that of a standard additive model.