{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:28:56Z","timestamp":1783650536316,"version":"3.55.0"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States Department of Agriculture\u2019s Animal and Plant Health Inspection Service"},{"name":"USDA-MIS-Animal and Plant Health Inspection Service","award":["AP17VSSPRS00C126"],"award-info":[{"award-number":["AP17VSSPRS00C126"]}]},{"name":"USDA-MIS-Animal and Plant Health Inspection Service","award":["AP19VSCEAH00C029"],"award-info":[{"award-number":["AP19VSCEAH00C029"]}]},{"DOI":"10.13039\/100004930","name":"Texas Parks and Wildlife Department","doi-asserted-by":"publisher","award":["475613"],"award-info":[{"award-number":["475613"]}],"id":[{"id":"10.13039\/100004930","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Chronic Wasting Disease Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite implementation of enhanced management practices, chronic wasting disease in US white-tailed deer (Odocoileus virginianus) continues to expand geographically. Herein, we perform the largest genome-wide association analysis to date for chronic wasting disease (n\u2009=\u2009412 chronic wasting disease-positive; n\u2009=\u2009758 chronic wasting disease-nondetect) using a custom Affymetrix Axiom single-nucleotide polymorphism array (n\u2009=\u2009121,010 single-nucleotide polymorphisms), and confirm that differential susceptibility to chronic wasting disease is a highly heritable (h2=\u00a00.611\u00a0\u00b1\u00a00.056) polygenic trait in farmed US white-tailed deer, but with greater trait complexity than previously appreciated. We also confirm PRNP codon 96 (G96S) as having the largest-effects on risk (P\u2009\u2264\u20093.19E-08; phenotypic variance explained \u2265 0.025) across 3 US regions (Northeast, Midwest, South). However, 20 chronic wasting disease-positive white-tailed deer possessing codon 96SS genotypes were also observed, including one that was lymph node and obex positive. Beyond PRNP, we also detected 23 significant single-nucleotide polymorphisms (P-value \u2264 5E-05) implicating \u226524 positional candidate genes; many of which have been directly implicated in Parkinson\u2019s, Alzheimer\u2019s and prion diseases. Genotype-by-environment interaction genome-wide association analysis revealed a single-nucleotide polymorphism in the lysosomal enzyme gene ARSB as having the most significant regional heterogeneity of effects on chronic wasting disease (P\u2009\u2264\u20093.20E-06); with increasing copy number of the minor allele increasing susceptibility to chronic wasting disease in the Northeast and Midwest; but with opposite effects in the South. In addition to ARSB, 38 significant genotype-by-environment single-nucleotide polymorphisms (P-value \u2264 5E-05) were also detected, thereby implicating \u2265 36 positional candidate genes; the majority of which have also been associated with aspects of Parkinson\u2019s, Alzheimer\u2019s, and prion diseases.<\/jats:p>","DOI":"10.1093\/g3journal\/jkac109","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T14:40:22Z","timestamp":1652193622000},"source":"Crossref","is-referenced-by-count":8,"title":["Genotype by environment interactions for chronic wasting disease in farmed US white-tailed deer"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7104-0032","authenticated-orcid":false,"given":"Christopher M","family":"Seabury","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathobiology, Texas A&M University , College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell A","family":"Lockwood","sequence":"additional","affiliation":[{"name":"Texas Parks and Wildlife Department , Austin, TX 78744, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A","family":"Nichols","sequence":"additional","affiliation":[{"name":"USDA-APHIS-VS-Cervid Health Program , Fort Collins, CO 80526-8117, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"issue":"8","key":"2022070613572445600_jkac109-B1","doi-asserted-by":"crossref","first-page":"e1005073","DOI":"10.1371\/journal.ppat.1005073","article-title":"Double-edge sword of sustained ROCK activation in prion diseases through neuritogenesis defects and prion accumulation","volume":"11","author":"Alleaume-Butaux","year":"2015","journal-title":"PLoS 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