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

Abstract

Gene expression is a dynamic phenotype influenced by tissue-specific regulatory mechanisms, which can modulate expression directly or indirectly through cis or trans factors. Identifying genetic variants in these regulatory regions can improve both expression quantitative trait locus (eQTL) mapping and gene expression prediction. Whole genome sequences offer the possibility for enhanced eQTL mapping accuracy, but detecting causal variants remains challenging. Here, 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 expression for three pig breeds. Functional annotations from early developmental stages improved eQTL mapping interpretability as shown by the enrichment of trait-relevant QTLs. However, despite the use of functional annotations, predictions across breeds remain challenging due to differences in genetic architectures. Our work contributes to the understanding of gene expression regulation in livestock and highlights the value of functional annotations, despite continued challenges for predictions across breeds. HighlightsO_LIMatched whole-genome sequences and expressions reveal transcriptional regulatory variants. C_LIO_LIEarly epigenetic marks can guide transcriptome prediction and eQTL mapping. C_LIO_LIAnnotation-guided models can enhance the interpretability of eQTL mapping. C_LIO_LIPorting predictions across pig breeds remains challenging even with annotations. C_LIO_LIA case study linked IGF2 liver eQTLs with annotations and cholesterol QTLs. C_LI