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

Abstract

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. 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. 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.