Genome-wide association studies of calf resilience traits derived from milk intake variability in Holstein calves.

Abstract

Understanding and genetically improving dairy calf resilience is critical for enhancing health, welfare, and productivity of dairy animals under increasing environmental and disease pressures. In this study, we conducted genome-wide association studies (GWAS) to identify genetic variants and genomic regions associated with calf resilience traits derived from automated milk feeder (AMF) records in American Holstein calves. Data from 14,749 calves, including milk intake, milk drinking behavior, and calf health records, were available for the analyses. The pedigree records included 21,630 animals, with genomic data available for 9,273 calves and 57,128 single nucleotide polymorphisms (SNP) after quality control. A range of resilience indicators were defined based on deviations from the theoretical (expected) cumulative milk intake curves, using nonlinear modeling and perturbation analyses to characterize individual calf responses to environmental and health-related stressors. The derived calf resilience traits included amplitude, perturbation time (duration), recovery time, area between observed and expected curves, recovery ratio, and autocorrelation of deviations. The genomic analyses were performed using the BLUPF90 family of programs. We identified 26 SNPs located across 5 autosomal chromosomes, which were significantly associated with 6 calf resilience traits. The genes located near these SNPs were enriched for biological functions related to immune response, mitochondrial integrity, oxidative stress regulation, and protein homeostasis, including loci harboring key candidate genes such as ABCB8 (ATP Binding Cassette Subfamily B Member 8), NOS3 (Nitric Oxide Synthase 3), AGAP3 (ArfGAP With GTPase Domain, Ankyrin Repeat And PH Domain 3), and PRKAG2 (Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2). Functional enrichment analyses highlighted molecular functions and pathways related to nucleotide and ATP-dependent regulation, transporter and ion-channel activity, nitric oxide signaling, kinase-mediated regulation, and host-response pathways. Additionally, several significant SNPs were located within genomic regions previously associated with quantitative trait loci for economically important traits such as average daily gain and fertility, although further studies are needed to evaluate the genetic relationships between these traits and calf resilience. These findings provide foundational insights into the genetic basis of calf resilience, offering pathways for selective breeding to enhance animal adaptability and welfare in modern dairy production systems.