Integrating genome-wide association study and haplotype-resolved epigenomes reveals complex parent-of-origin effects in pigs

Background Parent-of-origin effects (POEs) violate the assumption of additive genetic models by allowing allelic effects to depend on parental origin, yet their mechanistic basis remains incompletely understood. Results Here, we combine genome-wide POE mapping in an F2 Eurasian pig population with haplotype-resolved transcriptomes and epigenomes from reciprocal crosses. We uncover widespread POEs affecting growth traits, many outside canonical imprinted regions, indicating that canonical imprinting explains only a subset of parent-of-origin-dependent variation. We recapitulate known imprinting effects at loci such as IGF2 and KCNQ1 , and link distal POE loci for rib length to IGF2 by long-range chromatin interactions. Strikingly, some POEs emerge from parent-specific 3D chromatin architecture, independent of allele-specific expression or histone marks. Cross-species comparisons nominate additional candidate imprinted genes. Conclusions Together, our results reveal POEs as pervasive and mechanistically diverse, and show chromatin topology as a plausible candidate mechanism of parental-origin regulation, reshaping our understanding of complex trait inheritance.