Gene variants in the pheromone vomeronasal receptors and QTLs around behavioral and fat metabolism genes associated with altered feed efficiency in cattle

Authors: SHIRAK, ANDREY - Agricultural Research Organization Of Israel (ARO); YANG, LIU - University Of Maryland; Bhowmik, Nayan; BEN-MEIR, YEHOSHAV - Agricultural Research Organization Of Israel (ARO); SHABTAY, ARIEL - Agricultural Research Organization Of Israel (ARO); COHEN-ZINDER, MIRI - Agricultural Research Organization Of Israel (ARO); Baldwin, Ransom; SEROUSSI, EYAL - Agricultural Research Organization Of Israel (ARO); Liu, Ge; GERSHONI, MORAN - Agricultural Research Organization Of Israel (ARO)

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/21/2026
Publication Date: 2/5/2026
Citation: Shirak, A., Yang, L., Bhowmik, N., Ben-Meir, Y.A., Shabtay, A., Cohen-Zinder, M., Baldwin, R.L., Seroussi, E., Liu, G., Gershoni, M. 2026. Gene variants in the pheromone vomeronasal receptors and QTLs around behavioral and fat metabolism genes associated with altered feed efficiency in cattle. Scientific Reports. https://doi.org/10.1038/s41598-026-37314-3.
DOI: https://doi.org/10.1038/s41598-026-37314-3

Interpretive Summary: Making cattle more efficient at using feed is important for lowering costs and reducing environmental impact. However, it is difficult to select more efficient cattle due to a lack of known selection markers. To address this, we studied genetic and feed efficiency data from two different herds and identified nine genetic markers linked to feed efficiency. One important discovery was a variation in the VN1R1 gene, which influences appetite and metabolism. These findings provide potential markers to breed more efficient cattle in the future. This information from this research will benefit scientists in the effort improve genetic selection strategies to reduce feed costs and environmental impact for dairy farmers and the industry.

Technical Abstract: Improving feed efficiency in cattle is increasingly important for both environmental and economic reasons. Although feed efficiency traits are under considerable genetic control, with an average moderate heritability estimate of 0.33, genetic evaluations are limited by the difficulties in measuring feed intake and the lack of records from most commercial herds. Most genetic evaluations rely on small numbers of records from research farms, resulting in under-represented genetic variation and pronounced sampling errors in heritability estimates. The low genetic variation and constant environment in research herds suggest that additional mechanisms, such as epigenetic regulation, contribute to phenotypic variation. To enhance the discovery of genetic mechanisms underlying feed efficiency and to address measurement limitations and the under-representation of genetic variation, we used joint phenotypic and genotypic measurements from two distinct herds for GWAS and in-depth genomic analysis. By applying this approach, we discovered nine significant markers with effects on Residual Feed Intake (RFI) ranging from -5.9 to 1.91. QTL enrichment analysis specifically pointed to traits that compose RFI, including DMI and protein yield. Gene enrichment analysis directed us to the vomeronasal pheromone receptor cluster (VN1R1 on BTA18), behavioral response (GRIK2 on BTA9; ANKFN1 on BTA19), and fat metabolism genes (KIF5C on BTA2; SV2B on BTA21). Of these candidate genes, likely functional AA variations were observed only in the VN1R1 putative protein (314 AA) after screening a sample of 27 Israeli Holstein genomes. These functional variations included two truncation mutations that were capable of encoding 89 and 239 AA polypeptides. Consistent with these findings, whole-genome sequence data analysis of RFI-characterized Irish bulls identified a significant association between the 89 AA truncation and high RFI, further validating our results and indicating that although such variation was common, the presence of an intact VN1R1 receptor was associated with a beneficial effect on feed efficiency. Moreover, the 89 AA truncation was observed in diverse cattle breeds, including American, Israeli, Irish, and New Zealand Holstein. These findings are compatible with feed efficiency being a complex trait governed by neural (behavioral) and metabolic components. Further characterization of these factors would allow genetic selection to reduce feed costs and environmental footprints.