Phasing parental genomes of hybrid pigs facilitates the deciphering of imprinted genes and the mechanistic basis of heterosis

Conventional genetic models assume symmetric parental contributions, masking parent-of-origin effects underlying heterosis. Here, we integrate haplotype-resolved genomic and transcriptomic data from 594 F2 pigs to quantify parent-of-origin effects. We develop a phased analytical framework that overcomes the limitations of additive models, enabling systematic dissection of allelic regulatory asymmetry. This approach reveals widespread cis-regulatory divergence between parental genomes, identifying 1231 non-additive cis-eGenes enriched for upstream transcriptional regulators, 138 highly biased genes, and 15 imprinted genes, including two candidates supported by epigenetic validation. Critically, phased mapping shows that heterosis reflects complementary parental strategies: growth traits are predominantly driven by paternally inherited alleles, whereas reproductive success shows a maternal bias, with candidate genes including B3GALT4, MAPK14, and DST for growth and CMTR1 for reproduction. These findings support a “parental complementary advantage” model of heterosis, where paternal and maternal genomes contribute distinct but complementary effects to growth and reproduction. Our study provides a haplotype-aware framework for understanding parent-of-origin regulation and heterosis in livestock. A study integrates haplotype-resolved genomic and transcriptomic data from a hybrid F2 pig population to investigate imprinted genes, parent-of-origin effects, and heterosis, providing an analytical framework for understanding asymmetric parental genome contributions to gene expression.