A multi-tissue atlas of allelic specific expression in cattle

Allele-specific expression (ASE) analysis is a valuable tool for validating expression quantitative trait loci (eQTLs), identifying causal variants associated with complex traits, and exploring the genetic mechanisms underlying heterosis. However, few studies have investigated the connections between these elements. In this study, we characterized ASE variants across 35 tissues using 7,532 publicly available RNA-seq datasets and found that ASE variants exhibited stronger tissue specificity and lower reproducibility compared to eQTLs. Interestingly, ASE variants with opposite directional effects showed greater resilience across diverse environments. Functional annotation with epigenomic data revealed that ASE variants were mainly located in enhancer regions and implicated in post-transcriptional and translational processes. Our analysis of eQTLs, splicing QTLs (sQTLs), and QTLs associated with milk-related traits in Holstein cattle, combined with enrichment analysis and effect size evaluation, showed that ASE variants were more strongly associated with dominant effects than additive effects, particularly in reproductive and immune-related tissues/traits, which exhibited higher heterosis. These findings enhance our understanding of the genetic mechanisms underlying heterosis and ASE and provide valuable regulatory variants that can be used to improve economic traits through molecular breeding or strategic exploitation of heterosis in cattle.