Genome wide association study of thyroid hormone levels following challenge with porcine reproductive and respiratory syndrome virus

Authors: Van Goor, Angelica; PASTERNAK, ALEX - Purdue University; WALUGEMBE, MUHAMMAD - Iowa State University; Chehab, Nadya; HAMONIC, GLENN - University Of Saskatchewan; DEKKERS, JACK - Iowa State University; HARDING, JOHN - University Of Saskatchewan; Lunney, Joan

Submitted to: Frontiers in Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/25/2023
Publication Date: 2/9/2023
Citation: Van Goor, A.G., Pasternak, A., Walugembe, M., Chehab, N.L., Hamonic, G., Dekkers, J., Harding, J., Lunney, J.K. 2023. Genome wide association study of thyroid hormone levels following challenge with porcine reproductive and respiratory syndrome virus. Frontiers in Genetics. 14. Article 1110463. https://doi.org/10.3389/fgene.2023.1110463.
DOI: https://doi.org/10.3389/fgene.2023.1110463

Interpretive Summary: Here we report, for the first time, genomic control of serum thyroid hormone levels in both piglets and fetuses during porcine reproductive and respiratory syndrome virus (PRRSV) infection. These hormone levels were lowly to moderately heritable in piglets and fetuses. We used detailed genomic methods to identify the genetic quantitative trait loci and the nearby putative candidate genes that have biological connections especially for immune-related activities. These genes are good candidates for future investigations into the complex interaction of thyroid hormones and animal health. Importantly, these results advance our understanding of both piglet and fetal response to PRRSV infection by characterizing the genomic control of a novel phenotype (thyroid hormone levels) associated with host resilience and susceptibility.

Technical Abstract: Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory disease in piglets and reproductive disease in sows. Piglet and fetal serum thyroid hormone (i.e., T3 and T4) levels decrease rapidly in response to Porcine reproductive and respiratory syndrome virus infection. However, the genetic control of T3 and T4 levels during infection is not completely understood. Our objective was to estimate genetic parameters and identify quantitative trait loci (QTL) for absolute T3 and/or T4 levels of piglets and fetuses challenged with Porcine reproductive and respiratory syndrome virus. Methods: Sera from 5-week-old pigs (N = 1792) at 11 days post inoculation (DPI) with Porcine reproductive and respiratory syndrome virus were assayed for T3 levels (piglet_T3). Sera from fetuses (N = 1,267) at 12 or 21 days post maternal inoculation (DPMI) with Porcine reproductive and respiratory syndrome virus of sows (N = 145) in late gestation were assayed for T3 (fetal_T3) and T4 (fetal_T4) levels. Animals were genotyped using 60 K Illumina or 650 K Affymetrix single nucleotide polymorphism (SNP) panels. Heritabilities, phenotypic correlations, and genetic correlations were estimated using ASREML; genome wide association studies were performed for each trait separately using Julia for Whole-genome Analysis Software (JWAS). Results: All three traits were low to moderately heritable (10%–16%). Phenotypic and genetic correlations of piglet_T3 levels with weight gain (0–42 DPI) were 0.26 ± 0.03 and 0.67 ± 0.14, respectively. Nine significant quantitative trait loci were identified for piglet_T3, on Sus scrofa chromosomes (SSC) 3, 4, 5, 6, 7, 14, 15, and 17, and collectively explaining 30% of the genetic variation (GV), with the largest quantitative trait loci identified on SSC5, explaining 15% of the genetic variation. Three significant quantitative trait loci were identified for fetal_T3 on SSC1 and SSC4, which collectively explained 10% of the genetic variation. Five significant quantitative trait loci were identified for fetal_T4 on SSC1, 6, 10, 13, and 15, which collectively explained 14% of the genetic variation. Several putative immune-related candidate genes were identified, including CD247, IRF8, and MAPK8. Discussion: Thyroid hormone levels following Porcine reproductive and respiratory syndrome virus infection were heritable and had positive genetic correlations with growth rate. Multiple quantitative trait loci with moderate effects were identified for T3 and T4 levels during challenge with Porcine reproductive and respiratory syndrome virus and candidate genes were identified, including several immune-related genes. These results advance our understanding of growth effects of both piglet and fetal response to Porcine reproductive and respiratory syndrome virus infection, revealing factors associated with genomic control of host resilience.