Guiding eQTL mapping and genomic prediction of gene expression in three pig breeds with tissue-specific epigenetic annotations from early development

Gene expression is a dynamic phenotype influenced by tissue-specific regulatory mechanisms, including promoters, enhancers, and repressors, often located in non-coding genomic regions. Regulatory sequences can modulate gene expression directly through cis factors or indirectly via trans factors. Identifying genetic variants, such as single nucleotide polymorphisms (SNPs), in these regulatory regions can improve both expression quantitative trait locus (eQTL) mapping and gene expression prediction. The use of whole genome sequencing (WGS) data offers the possibility for enhanced eQTL mapping accuracy, but the detection of causal variants remains challenging. In this study, we evaluate the potential added-value of integrating tissue-specific epigenetic annotations, such as chromatin accessibility and methylation status, into within-breed genomic predictions of gene expression for three distinct pig breeds: Duroc, Landrace, and Large White. By incorporating functional annotations from early developmental stages, we demonstrated improved eQTL mapping interpretability and highlighted the enrichment of trait-relevant QTLs. However, while functional annotations improved the interpretability of eQTL mapping within breeds, predictions across breeds remain challenging due to differences in genetic architectures and linkage disequilibrium. Our work contributes to the understanding of gene expression regulation in livestock and suggests that incorporating functional annotations into genomic prediction models holds promise for targeting causal mutations, despite continued challenges for predictions across breeds.