Accurate Genomic Predictions for Chronic Wasting Disease in U.S. White-Tailed Deer

The geographic expansion of chronic wasting disease (CWD) in U.S. white-tailed deer (<i>Odocoileus virginianus</i>) has been largely unabated by best management practices, diagnostic surveillance, and depopulation of positive herds. Using a custom Affymetrix Axiom single nucleotide polymorphism (SNP) array, we demonstrate that both differential susceptibility to CWD, and natural variation in disease progression, are moderately to highly heritable ([Formula: see text] among farmed U.S. white-tailed deer, and that loci other than <i>PRNP</i> are involved. Genome-wide association analyses using 123,987 quality filtered SNPs for a geographically diverse cohort of 807 farmed U.S. white-tailed deer (n = 284 CWD positive; n = 523 CWD non-detect) confirmed the prion gene (<i>PRNP</i>; G96S) as a large-effect risk locus (<i>P</i>-value < 6.3E-11), as evidenced by the estimated proportion of phenotypic variance explained (PVE ≥ 0.05), but also demonstrated that more phenotypic variance was collectively explained by loci other than <i>PRNP</i> Genomic best linear unbiased prediction (GBLUP; n = 123,987 SNPs) with <i>k</i>-fold cross validation (<i>k</i> = 3; <i>k</i> = 5) and random sampling (n = 50 iterations) for the same cohort of 807 farmed U.S. white-tailed deer produced mean genomic prediction accuracies ≥ 0.81; thereby providing the necessary foundation for exploring a genomically-estimated CWD eradication program.