Genetic analysis of stress hormone levels in hair of healthy nursery pigs and their relationships with backtest responses

This study explored the genetics of the levels of stress hormones (cortisol, cortisone, DHEA, and DHEA-S) in hair of 863 clinically healthy Yorkshire × Landrace male pigs at ∼40 days of age and evaluated their potential as biomarkers of innate stress response by estimating genetic correlations with responses to a 30 s backtest performed at ∼27 days of age. Backtest responses included the number and intensity of vocalizations (VN and VI) and struggles (SN and SI). With pigs genotyped using a 50 K single nucleotide polymorphism (SNP) panel that was imputed to 650 K SNPs, heritability estimates for the levels of cortisol, cortisone, DHEA, and DHEA-S were 0.33, 0.04, 0, and 0.31, respectively, while those for backtest responses ranged from 0.26 to 0.57. Litter effects accounted for 9 to 16% of the phenotypic variance for stress hormone levels and none for backtest responses. Genetic correlation estimates among stress hormone levels were strongest between cortisol and cortisone (0.99 ± 0.12), while those among backtest responses ranged from 0.60 to 0.99. Cortisol was estimated to have moderate genetic correlations with VN (0.24 ± 0.19) and VI (0.50 ± 0.24) but not with SN and SI. Genome-wide association studies identified a major quantitative trait locus (QTL) for hair cortisol levels near the glucocorticoid receptor gene (NR3C1) that explained 45.3% of the genetic variance and that may be different than a causative mutation that was previously identified in this gene for cortisol levels in porcine blood. An extra copy of the minor allele (frequency = 9%) at the lead SNP for this QTL, rs341258564 originated from both parental breeds and reduced levels of cortisol by 30 ± 6% and of cortisone by 17 ± 4%, and increased VN by 5 ± 2%. Additional QTL with smaller effects (1.0 to 11.1% of genetic variance) were identified for DHEA-S, cortisol/DHEA-S, cortisone/DHEA-S, VI, and VN. Ranked gene set enrichment analyses of 0.25 Mb windows based on genetic variance explained showed that windows associated with glucocorticoid levels were enriched for biological terms related to energy production and suppression of inflammation. In contrast, those associated with DHEA-S were enriched for biological processes related to immunity activation and gene transcriptional and post-transcriptional regulation. These findings establish the genetic basis of stress response in young and clinically healthy pigs, identify the genomic location of a major QTL for hair cortisol levels, and show that cortisol levels in hair of young and healthy pigs are potential genetic biomarkers for the innate coping response style of pigs to noninfectious stressors. These results open avenues that can facilitate selection of pigs that cope better with noninfectious stressors.