We were able to replicate the association in three commercial pig populations with different breed origins. SNP c.1829C>T, leading to a p.Ala610Val substitution in the ligand binding domain, showed large (about 0.6× and 1.2× phenotypic standard deviations for cortisol level and adrenal weight, respectively), and highly significant (2.1E-39≤log10(1/p)≤1.7E+0) negative effects on both traits. To determine the causal variant(s), we resequenced the coding region of NR3C1 and found three missense single nucleotide polymorphisms (SNPs). We detected a major quantitative trait locus at the position of the glucocorticoid receptor gene ( NR3C1) – a key regulator of HPA axis activity. To identify loci affecting regulation of the hypothalamic-pituitary-adrenal (HPA) axis in the pig we performed a genome-wide association study for two parameters of acute and long-term adrenal activity: plasma cortisol level and adrenal weight.
Glucocorticoids produced in the adrenal cortex under the control of the hypothalamic-pituitary axis play a vital role in the maintenance of basal and stress-related homeostasis and influence health and well-being.
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