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

Angelica Van Goor; Alex Pasternak; Muhammed Walugembe; Nadya Chehab; Glenn Hamonic; Jack C M Dekkers; John C S Harding; Joan K Lunney

doi:10.3389/fgene.2023.1110463

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

Front Genet. 2023 Feb 9:14:1110463. doi: 10.3389/fgene.2023.1110463. eCollection 2023.

Authors

Angelica Van Goor¹, Alex Pasternak², Muhammed Walugembe³, Nadya Chehab¹, Glenn Hamonic⁴, Jack C M Dekkers³, John C S Harding⁴, Joan K Lunney¹

Affiliations

¹ Animal Parasitic Diseases Laboratory, United States Department of Agriculture, Agricultural Research Services, Beltsville Agricultural Research Center, Beltsville, MD, United States.
² Department of Animal Science, Purdue University, West Lafayette, IN, United States.
³ Department of Animal Science, Iowa State University, Ames, IA, United States.
⁴ Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

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.

Keywords: disease resistance; fetal pig; growing pig; hypothyroidism; immunity; porcine reproductive and respiratory syndrome; quantitative trait loci; thyroid hormones.

Grants and funding

This study was funded by the research on the piglets was provided by efforts of the PHGC from the US National Pork Board (NPB) (#07-233, #09-208, #09-244, and #10-033). Pigs were generously supplied by swine breeding companies Genus PIC plc, Newsham/Choice Genetics, FAST Genetics, Genetiporc, Genesus, Topigs Norsvin and PigGen Canada, Inc. Members. Support from the PRRS Coordinated Agricultural Project (PRRS-CAP), USDA-NIFA Award #2008-55620-19132, covered SNP genotyping. Additional PHGC infection, vaccination and field trials have been funded by Genome Canada project #2209_F; and USDA-NIFA Translational Genomics grant # 2013-68004-20362. Additional support has come from the USDA sponsored National Research Support Project 8 (NRSP-8: National Animal Genome Research Program, 2022) Swine Genome and Bioinformatics research programs, and from Kansas State University and USDA ARS 1245-32000-098 and 8042-32000-102 projects. Funding to support the research on the fetal samples was provided by USDA ARS (project 8042–32000-102) to JL, the SCINet project of the USDA ARS project number 0500-00093-001-00-D, and AVG was supported by a USDA ARS Headquarters Postdoctoral Fellowship. Major support for the fetal PRRS studies was from Genome Canada (Project 2014LSARP_8202), Genome Prairie (Project 346143) with administrative support from Genome Alberta, and industry support from PigGen Canada to JH. The industry partners and funding bodies played no role in the design of the studies, in collection, analyses, interpretation of results, or preparation of the manuscript.