ABSTRACT: Milk protein percentage (PP) and fat percentage (FP) are important indicators for measuring milk quality, but only a few causative genes such as DGAT1, GHR, and ABCG2, have been identified, indicating substantial potential for further exploration. Here, we integrated genotyping, RNA-seq, ATAC-seq, single-cell atlas and cis-QTLs datasets from the liver and mammary gland to investigate their genetic regulation. We identified cell type affecting milk composition, such as HPE2 and LumSec-HSPH1, and highlighted nine candidate genes (EFNA1, ERBB3, DUSP16, DEPTOR, TRIM46, HSTN, CIDEA, ACACA and SPP1) that are involved in the regulation of milk protein and fat synthesis through MAPK, AMPK, PI3K-Akt, and mTOR signalling pathways. Notably, EFNA1 was consistently identified across all omics analyses,
