Mapping multitissue regulatory variants reveals a liver-centric coexpression network associated with duck egg-laying performance

Poultry egg production is shaped by the intertwined action of multiple physiological systems, greatly magnifying the complexity of its underlying genetic regulation. Although multitissue mapping of regulatory variants offers a powerful route to untangle this complexity, comprehensive data sets in ducks remain scarce. Meanwhile, the contributions of peripheral systems beyond neuroendocrine regulation on poultry egg production are still largely unexplored. Here, we generate 979 RNA-seq samples from the liver, ovary, oviduct shell gland, and spleen, along with matched whole-genome sequencing data from 307 egg-laying ducks. We map cis -regulatory variants associated with gene expression (eQTL), alternative splicing (sQTL), and 3′ alternative polyadenylation (apaQTL), yielding 14,074, 6267, and 4994 genes with at least one significant eQTL, sQTL, and apaQTL, respectively. By integrating this resource and GWAS results, we confirm that ABCG2 expression in the shell gland specifically regulates eggshell color, with additional involvement of ENOPH1 ’s 3′APA sites in both the shell gland and liver. In addition, expression of LOC101800576 and LOC101790890 in the shell gland, of LOC119713219 in the ovary, and of GLP2R in the spleen is causally linked to declining egg production at peak laying. Last, we delineate a cross-tissue regulatory landscape underlying duck egg production and identify liver-derived modules, particularly Liver_ME1, which is mainly involved in cell cycle regulation, as central hubs coordinating with peripheral tissues affecting duck egg production. This work delivers a key resource and fresh perspectives for the genetic mechanism dissection of duck egg production and for future studies on cross-tissue regulation of reproduction.