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Gene Set Enrichment Analysis of Residual Feed Intake in Hereford Cattle
Feed comprises 66% and 77% of the total cost of calf and yearling finishing systems, respectively. Heritabilities for feed intake and feed efficiency (FE, estimated as residual feed intake, or RFI) have ranged from 0.08 to 0.46 in previous studies, highlighting the potential for selection to bring about significant gains in feed efficiency and profitability within the beef industry. The objective of this study was to identify gene pathways significant for FE as measured by RFI through the use of gene set enrichment analysis (GSEA) using single nucleotide polymorphisms (SNPs) as proxies for bovine genes. A population of 847 Hereford cattle (181 purebreds and 666 high-percentage Hereford crossbred animals consisting of 23 females and 824 males ranging in age from 210 to 496 days) from a single ranch were evaluated for a period ranging from 70 to 140 days on feed (DOF). Only 31 animals were fed over 72 days. Average daily gain (ADG), dry matter intake (DMI), initial weight (IW), mid-test metabolic weight (MMWT), and DOF were recorded across the feeding period for each individual. Covariates for the genome wide association study (GWAS) consisted of age, sex, DOF and % Hereford. GWAS was followed by GSEA of SNP data with Bos taurus gene sets sourced from GO, KEGG, Panther, Reactome, and Metacyc. Gene sets containing fewer than 10 or greater than 200 SNPs were excluded from the analysis. A total of 19,598 bovine genes were mapped within gene sets, and proxy SNPs were mapped to genes located within 20 kilobase pairs. The null distribution of the GSEA test statistic was approximated using 10,000 random permutations. Genotypes were obtained from the Illumina BovineSNP50 (N = 361) and BovineHD (N = 486) BeadChips and imputed to 778,000 SNPs using Beagle. The GO pathway GO:0044706 multi-multicellular organism process with 90 genes was significant for RFI with an false discovery rate of 0.061 and a normalized enrichment score of 3.978. There were a total of 51 leading edge genes in GO:0044706. The top 10 genes were: PGR, CORIN, STAT5B, TIMP1, PCSK5, THRB, NR2F2, MMP2, FKBP4, and JUNB. Heritability for RFI was estimated to be 0.49. These results suggest that genetic selection for RFI has potential to dramatically affect the efficiency and, therefore, profitability of beef cattle production.
Keywords: genetics RFI beef