Genome-wide association study for the detection of genetic variants associated with the antibody response upon viral hemorrhagic septicemia virus vaccination in Paralichthys olivaceus.

Viral hemorrhagic septicemia virus (VHSV), a negative-sense single-stranded RNA virus in the Rhabdoviridae family, poses a significant threat to olive flounder (Paralichthys olivaceus) aquaculture. Genetic variation in antibody-mediated immune response is an important determinant of host resistance to VHSV. However, the genomic architecture underlying variation in antibody production following VHSV vaccination remains poorly characterized. In this study, a genome-wide association study (GWAS) was conducted to identify genetic loci and underlying regulatory mechanisms associated with VHSV vaccination-induced antibody production, with the ultimate aim of providing a foundation for developing virus-resistant P. olivaceus strains. Initially, 576 P. olivaceus individuals were intraperitoneally vaccinated with a dose of 1 × 107.5 TCID50 of formalin-inactivated VHSV. Blood samples were collected 21 days post-vaccination to measure VHSV-induced fold antibody response as the target phenotype using an enzyme-linked immunosorbent assay (ELISA). Genomic DNA was extracted from fin samples and genotyped using a 70 K Affymetrix® Axiom® myDesign™ array. After quality control filtration, 55,758 high-quality single-nucleotide polymorphisms (SNPs) from 558 individuals were retained for GWAS. The association analysis identified one statistically significant SNP on chromosome 9 that exceeded the Bonferroni threshold (p < 1 × 10-6), which is annotated to the Ephrin type-B receptor 4b (ephb4b) gene. The estimated heritability of the VHSV-induced fold antibody response trait was 0.189. Functional gene annotation of the top-most associated SNP markers indicated their involvement in intercellular interaction, migration, and tissue organization of immune cells during immune regulation. Collectively, these findings elucidate the genetic architecture of VHSV-induced fold antibody response in P. olivaceus and establish a basis for the genomic selection breeding programs.