Integrated analysis of GWAS and molQTLs reveals cell-specific genetic variants in the porcine immune system

Pigs are vital to global agriculture, and infectious diseases cause significant economic losses. Leukocytes provide a critical window into the genetic regulation of pig immune traits. However, understanding of these mechanisms within specific immune cell types remains insufficient. Here, we integrate 11 immune traits and systematically map the regulatory landscapes of expression quantitative trait loci (eQTLs), splicing QTLs (sQTLs), and alternative polyadenylation QTLs (apaQTLs) in porcine peripheral blood mononuclear cells (PBMCs) and neutrophils to uncover cell type-specific patterns. These molecular QTLs (molQTLs) exhibit strong cell-type specificity and preferentially regulate genes involved in cross-cell communication that are linked to core immunity, thereby shaping immune phenotypes through intercellular networks. Furthermore, we identify 588 molQTLs that colocalize with genome-wide association study signals for phagocytic capacity. Among these, 60.3% of apaQTLs independently modulate immune traits, including the variant rs330263631. Experiments confirm that rs330263631 modulates mRNA stability and expression levels of the TXNDC15 by dynamically selecting polyadenylation sites and altering the length of the 3' untranslated region. This work systematically delineates the PBMC- and neutrophil-specific genetic architecture underlying immune regulation in pigs and provides a molecular foundation for deciphering the genetic mechanisms of porcine immune traits.