Background: Chickens provide globally important livestock products. Understanding the genetic and molecular mechanisms underpinning chicken economic traits is crucial for improving their selective breeding. Influenced by a combination of genetic and environmental factors, metabolites are the ultimate expression of physiological processes and can provide key insights into livestock economic traits. However, the serum metabolite profile and genetic architecture of the metabolome in chickens have not been well studied. Results: Here, comprehensive metabolome detection was performed using non-targeted LC–MS/MS on serum from a chicken advanced intercross line (AIL). In total, 7,191 metabolites were used to construct a chicken serum metabolomics dataset and to comprehensively characterize the serum metabolism of the chicken AIL population. Regulatory loci affecting metabolites were identified in a metabolome genome-wide association study (mGWAS). There were 10,061 significant SNPs associated with 253 metabolites that were widely distributed across the entire chicken genome. Many functional genes affect metabolite synthesis, metabolism, and regulation. We highlight the key roles of TDH and AASS in amino acids, and ABCB1 and CD36 in lipids. Conclusions: We constructed a chicken serum metabolite dataset containing 7,191 metabolites to provide a reference for future chicken metabolome characterization work. Meanwhile, we used mGWAS to analyze the genetic basis of chicken metabolic traits and metabolites and to improve chicken breeding.

Chicken is a valuable model for understanding fundamental biology, vertebrate evolution and diseases, as well as a major source of nutrient-dense and lean-protein-enriched food globally. Although it is the first non-mammalian amniote genome to be sequenced, the chicken genome still lacks a systematic characterization of functional impacts of genetic variants. Here, through integrating 7,015 RNA-Seq and 2,869 whole-genome sequence data, the Chicken Genotype- Tissue Expression (ChickenGTEx) project presents the pilot reference of regulatory variants in 28 chicken tissue transcriptomes, including millions of regulatory effects on primary expression (including protein-coding genes, lncRNA and exon) and post-transcriptional modifications (alternative splicing and 3’ untranslated region alternative polyadenylation). We explored the tissue-sharing and context-specificity of these regulatory variants, their underlying molecular mechanisms of action, and their utility in interpreting adaptation and genome-wide associations of 108 chicken complex traits. Finally, we illustrated shared and lineage-specific features of gene regulation between chickens and mammals, and demonstrated how the ChickenGTEx resource can further assist with translating genetic findings across species. One-Sentence Summary: The ChickenGTEx provides a multi-tissue reference of regulatory variants for chicken genetics and genomics, functional genomics, precision breeding, veterinary medicine, vertebrate evolution and even human biomedicine.

Chicken is a valuable model for understanding fundamental biology and vertebrate evolution, as well as a major source of nutrient-dense and lean-protein-enriched food globally. Although it is the first non-mammalian amniote genome to be sequenced, the chicken genome still lacks a systematic characterization of functional variation. Here, through integrating bulk RNA-Seq of 7,015 samples, single-cell RNA-Seq of 127,598 cells and 2,869 whole-genome sequences, we presented an atlas of regulatory variants across 28 chicken tissues and 43 cell types, including millions of regulatory effects on primary expression (protein-coding genes, lncRNA and exon) and post-transcriptional modifications (alternative splicing and 3’ untranslated region alternative polyadenylation). We highlighted distinct molecular mechanisms underlying these regulatory variants and their context dependence and utility in interpreting genome-wide associations of 108 chicken complex traits. Finally, we illustrated lineage-specific features of gene regulation between chickens and mammals, and demonstrated how this resource can assist with cross-species gene mapping of complex traits.