Egg-laying ChickenGTEx resource deciphers context-specific regulatory effects on fertility traits

Characterization of the genetic and molecular architecture underlying egg production traits in chickens is essential for improving the rate of genetic gain through intensive artificial selection. Here, to explore the dynamic landscape of regulatory effects across egg-laying stages in chickens, we generated 1272 RNA-seq samples of four tissues, i.e., the hypothalamic-pituitary-ovarian axis and liver, and paired whole-genome sequence data from 358 hens. We detected 1008 genes with stage-specific regulatory effects in at least one tissue excluding the pituitary. Out of them, 12.60, 52.78 and 32.84% were mediated by alterations in cell type composition, transcriptional factor activity, and gene co-expression networks among laying stages, respectively. Out of 80 significant loci associated with egg production traits that were detected in a large population (n = 12,952), 37 and 5 colocalized by shared and stage-specific regulatory effects, respectively. Furthermore, orthologues of these colocalized genes are enriched for the heritability of reproductive traits in pigs, cattle, and humans. In summary, we provide a resource for understanding reproduction-relevant gene regulation and highlight the importance of context-specific regulatory effects in deciphering complex traits.