Genome-wide meta-analyses in 708,480 individuals shed light on the genetic conflict between productivity and fertility in dairy cattle

Milk production and female fertility are negatively correlated in cattle, reducing the efficiency of artificial selection. The genomic loci underlying these antagonistic effects are unknown. We carried out one of the largest cattle meta-analyses of genome-wide association studies (Meta-GWAS) for 10 milk production and fertility traits in 12 breeds numbering 281,841 animals. The quantitative trait loci (QTL) regions identified were validated in an additional dataset of 426,639 animals. Up to 595 QTL per trait were confirmed across traits, including regions with both antagonistic and synergistic effects between milk yield, protein yield, and fertility. Combining GWAS results with functional genomic information highlighted candidate variants in several genes ( ABO, PAEP, LIF, ESR2, GC, and LALBA ). The large Holstein population dominated the Meta-GWAS and negatively influenced QTL discovery in smaller breed groups. These results reveal the genetic basis of milk-fertility trade-off and pave the way for more balanced cattle selection.