Multi‐Tissue Genetic Regulation of RNA Editing in Pigs

ABSTRACT RNA editing introduces transcriptomic variation and may contribute to complex trait regulation. However, its genetic determination in pigs remains unclear. Here, using 5457 PigGTEx RNA‐seq samples across 34 porcine tissues, we construct a comprehensive RNA editome and map 49 614 cis‐editing quantitative trait loci (edQTLs). These edQTLs define a distinct regulatory layer, with over 32% acting independently of expression or splicing QTLs (eQTLs/sQTLs). Crucially, edQTLs are significantly enriched in GWAS loci for 33 complex traits and show a superior contribution to heritability over eQTLs/sQTLs in some traits like growth and reproduction. Colocalization analyses pinpoint diverse causal mechanisms, revealing both edQTL‐specific effects (e.g., ERCC5 ) and coordinated events where single variants pleiotropically modulate RNA editing, splicing, and gene expression. Human‐pig comparative analysis identifies hundreds of evolutionarily conserved editing events linked to fundamental neurological pathways. This study provides the first comprehensive multi‐tissue porcine RNA editome and edQTL map, establishing RNA editing as a key mechanism linking genetic variation to phenotypic diversity in a major agricultural species and offering a valuable resource for future functional genomics research.