A Recursive Model Approach to Include Epigenetic Effects in Genetic Evaluations Using Simulated DNA Methylation Effects.

Abstract

The advancement of epigenetics has highlighted DNA methylation as an intermediate-omic influencing gene regulation and phenotypic expression. With emerging technologies enabling the large-scale and affordable capture of methylation data, there is growing interest in integrating this information into genetic evaluation models for animal breeding. This study used methylome information from six dairy cows to simulate the methylation profile of 13,183 genotyped animals. The liability to methylation was treated as an additive trait, while a trait moderated by methylation effects was also simulated. A multiomic model (GOBLUP) was adapted to incorporate methylation data in genomic and genetic evaluations, using the traditional BLUP method as a benchmark. The GOBLUP accurately recovered heritability estimates for the liability to methylation in all low, medium and high heritability scenarios and was consistent at estimating the heritability for the epigenetics-moderated trait of interest at a low-medium heritability of 0.14. The genetic variance recovered by the BLUP model was influenced by the h² of the liability to methylation, and a part of the methylation variance for the phenotypic trait was captured as additive. The h² of the phenotypic trait partially relies on the h² value for the methylation windows in the traditional model. A newly proposed estimated epigenetic value (EEV) combines the traditional additive genetic information from genotyping arrays with epigenetic information. The correlation between the traditional estimated breeding value (EBV) and EEV was high (0.92-0.99 depending on the scenario), but the correlation of the EEV with the true breeding value was higher than the correlation between the traditional EBV and the TBV (0.85 vs. 0.75, 0.71 vs. 0.66 and 0.61 vs. 0.62 depending on the scenario). This study demonstrates that the GOBLUP multiomic recursive model can effectively separates additive and epigenetic variances, enabling improved breeding decisions by accounting for genetic liability to DNA methylation. This enables more informed breeding decisions, optimising selection for desired traits. Emerging sequencing techniques offer new opportunities for cost-effective simultaneous acquisition of genetic and epigenetic data, further enhancing breeding accuracy.