RT Journal A1 Xi, Yang A1 Qi, Jingjing A1 Yang, Zhao A1 Zeng, Yutian A1 Zhang, Huicong A1 Tao, Qiuyu A1 Xu, Mengru A1 Huang, Anqi A1 Hu, Shenqiang A1 Han, Chunchun A1 Bai, Lili A1 Hu, Jiwei A1 Wang, Jiwen A1 Li, Liang A1 Fang, Lingzhao A1 Liu, Hehe T1 Mapping multitissue regulatory variants reveals a liver-centric coexpression network associated with duck egg-laying performance JF Genome Research JO Genome Research YR 2025 FD October 01 VO 35 IS 10 SP 2211 OP 2225 DO 10.1101/gr.280345.124 UL http://genome.cshlp.org/content/35/10/2211.abstract AB 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.