Genome-Wide Association Study and Differential Expression Analysis of Feed Efficiency using HD SNP Genotyping and Multiple Tissue RNAseq

Feed efficiency in beef cattle is a complex trait, influenced by many metabolic and physiological factors, and contributes to the profitability and sustainability of beef production. To identify genes influencing feed efficiency and related traits, sixteen progeny of two bull sires with divergent genomic breeding values for residual feed intake (RFI), a measure of feed efficiency, were treated as case-control in a genomic association study integrating dense phenotyping, high density SNP genotyping, and RNAseq of skeletal muscle, liver, adipose, pituitary, and duodenal tissues. Phenotyping for RFI was performed from weaning until slaughter, and additional traits phenotyped included body composition, feeding behavior, enteric methane production, and liver mitochondrial efficiency. Genome-wide association analysis of each phenotyped trait was performed using both Illumina BovineHD SNPs and variants detected in mRNA sequence (approx. 1.6M variants total). Significant variants were screened against those detected in sires’ whole genome sequence to identify those demonstrating patterns consistent with inheritance from the sire. Results were compared with differentially expressed genes in each tissue to determine common genes and gene pathways. Major gene functions implicated by GWAS and DE analysis included cellular assembly, function, and maintenance, cell-to-cell signaling and interaction, and lipid metabolism among others. Major pathways included the MAPK/ERK signaling pathway, the ubiquitination pathway, the complement system of the innate immune system, and the activation of various transmembrane active transporters. Combined assessment of GWAS and differential expression analysis provides enhanced characterization of the genetic mechanisms underpinning complex traits, facilitating identification of candidate genes for functional validation.