Accurate genomic predictions for chronic wasting disease in North American elk

The geographic expansion of chronic wasting disease (CWD) in North American elk (Cervus canadensis) has not been well mitigated by traditional best management practices, diagnostic surveillance, and depopulation of positive herds. Using a custom Affymetrix Axiom genetic variant array, we demonstrate that differential susceptibility to CWD is highly heritable (h2=0.630±0.061-0.678±0.056) among farmed North American elk, with loci other than PRNP involved. Genome-wide association analyses using 173,674 quality filtered variants for a geographically diverse cohort of 904 farmed North American elk (n = 357 CWD positive; n = 547 CWD nondetect) confirmed the prion gene (PRNP codon 132 Met→Leu and promoter variants) as a large-effect risk locus (P < 5.135E-08), as evidenced by the estimated proportion of phenotypic variance explained (PVE ≥ 0.032). However, more phenotypic variance was collectively explained by loci other than PRNP. Genomic best linear unbiased prediction (GBLUP; n = 173,674 markers) with k-fold cross-validation (k = 3; k = 5) and random sampling (n = 50 iterations) for the same cohort of 904 farmed North American elk produced mean genomic prediction accuracies ≥ 0.791, thereby providing a foundation to explore a genomically estimated CWD genetic improvement program.