Context-dependent genetic regulation of gene expression in pigs

Production livestock provide a natural system for studying gene regulation under physiologically demanding conditions shaped by rapid growth, environmental exposure, and immune challenges. Using farm pigs from the PigGTEx resource as a model, we applied quantile regression to uncover latent, context-dependent genetic effects on gene expression across tissues. This approach identifies quantile-specific expression quantitative trait loci (eQTLs) that are not detected by standard linear regression and are enriched in distal regulatory elements and three-dimensional genome architectural features rather than promoter-proximal regions. Genes with quantile-dependent eQTLs are more intolerant to loss-of-function variants and exhibit stronger enrichment in GO functional categories, indicating their likely functional significance. Cross-species comparisons reveal substantial overlap between pig and human eGenes across tissues, indicating conservation of regulatory architecture. Notably, many quantile-specific eQTLs influence tail expression states and involve genes relevant to human disease. For example, we identify a cis-eQTL affecting the conserved transcriptional regulator BCL6B in pig blood that modulates enhancer activity and reduces expression at lower quantiles. In contrast, BCL6B is minimally expressed in resting human blood and lacks detectable cis-regulatory variation under baseline conditions, consistent with its reported induction during immune activation. These findings demonstrate that pig eQTL maps can reveal context-dependent regulatory variation at loci that remain silent or weakly variable in human cohorts.