{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:30:11Z","timestamp":1791923411300,"version":"4.3.4"},"reference-count":19,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007917","name":"Agricultural Research Service","doi-asserted-by":"publisher","award":["5438-32000-033-00D"],"award-info":[{"award-number":["5438-32000-033-00D"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008114","name":"University of Nebraska-Lincoln","doi-asserted-by":"publisher","award":["2162390003"],"award-info":[{"award-number":["2162390003"]}],"id":[{"id":"10.13039\/100008114","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nebraska Beef Industry Endowment","award":["2662390323001"],"award-info":[{"award-number":["2662390323001"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    \u00a0Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2\u03b1, encoded by the endothelial PAS domain-containing protein 1 gene,\n                    <ns4:italic>EPAS1<\/ns4:italic>\n                    ) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate\n                    <ns4:italic>EPAS1<\/ns4:italic>\n                    haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    Paired samples of clinical cases and unaffected controls were collected at four feedlots in Nebraska and Wyoming. Each pair (n =102) was matched for source, pen, breed type, sex, arrival date, and management conditions. Cases were identified by animal caretakers, euthanized, and diagnosis was confirmed at necropsy. Cases were derived from 30 different ranch operations, with the largest source contributing 32. Animals were tested for eight\n                    <ns4:italic>EPAS1<\/ns4:italic>\n                    haplotypes encoding 36 possible different diploid combinations.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    The common, ancestral\n                    <ns4:italic>EPAS1<\/ns4:italic>\n                    haplotype encoding HIF2\u03b1 with alanine (A) at position 606 and glycine (G) at position 610 was equally frequent in cases and controls (0.67). The\n                    <ns4:italic>EPAS1<\/ns4:italic>\n                    variant haplotype reported to be associated with disease (encoding threonine (T) at position 606 and serine (S) at position 610) was not enriched in cases compared with controls (0.21 and 0.25, respectively). Frequencies of other\n                    <ns4:italic>EPAS1<\/ns4:italic>\n                    haplotypes (e.g., encoding Q270, L362, or G671) were each less than 0.05 overall. McNemar\u2019s test with 45 discordant pairs showed the linked T606\/S610 variant was not associated with BCHF (OR = 0.73, CI\n                    <ns4:sub>95<\/ns4:sub>\n                    0.38 -1.4,\n                    <ns4:italic>p<\/ns4:italic>\n                    -value = 0.37).\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    HIF2\u03b1 polypeptide variants were not significantly associated with BCHF in feedlot cattle at moderate altitudes. Thus, a wider search is needed to identify genetic risk factors underlying this disease.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.19951.1","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T08:50:07Z","timestamp":1564044607000},"page":"1189","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Evaluation of EPAS1 variants for association with bovine congestive heart failure"],"prefix":"10.12688","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1386-1208","authenticated-orcid":false,"given":"Michael P.","family":"Heaton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Bassett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Whitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta M.","family":"Krafsur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang In","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaden M.","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halden J.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline C.","family":"Pelster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Basnayake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale M.","family":"Grotelueschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0732-2590","authenticated-orcid":false,"given":"Brian L.","family":"Vander Ley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2019,7,25]]},"reference":[{"key":"ref-1","first-page":"3-24","article-title":"Brisket disease (dropsy of high altitude).","volume":"204","author":"G Glover","year":"1915","journal-title":"Colorado Agricultural Experiment Station."},{"key":"ref-2","first-page":"409-13","article-title":"Further Studies on brisket disease.","volume":"XV","author":"G Glover","year":"1918","journal-title":"Journal of Agricultural Records."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"171-83","DOI":"10.1016\/0002-9343(62)90288-7","article-title":"Brisket disease. III. Clinical features and hemodynamic observations in altitude-dependent right heart failure of cattle.","volume":"32","author":"H Hecht","year":"1962","journal-title":"Am J Med."},{"key":"ref-4","first-page":"515-7","article-title":"Brisket disease in yearling feedlot cattle.","volume":"169","author":"R Jensen","year":"1976","journal-title":"J Am Vet Med Assoc."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"326-34","DOI":"10.1111\/jvim.13789","article-title":"Right-Sided Congestive Heart Failure in North American Feedlot Cattle.","volume":"30","author":"J Neary","year":"2016","journal-title":"J Vet Intern Med."},{"key":"ref-6","doi-asserted-by":"publisher","DOI":"10.1177\/2045894018796804","article-title":"Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease.","volume":"9","author":"G Krafsur","year":"2019","journal-title":"Pulm Circ."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"509-522","DOI":"10.1177\/1040638719855108","article-title":"Investigation of congestive heart failure in beef cattle in a feedyard at a moderate altitude in western Nebraska.","volume":"31","author":"R Moxley","year":"2019","journal-title":"J Vet Diagn Invest."},{"key":"ref-8","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7863","article-title":"Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension.","volume":"6","author":"J Newman","year":"2015","journal-title":"Nat Commun."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.12688\/f1000research.9254.2","article-title":"Using diverse U.S. beef cattle genomes to identify missense mutations in EPAS1, a gene associated with pulmonary hypertension [version 2; peer review: 2 approved].","volume":"5","author":"M Heaton","year":"2016","journal-title":"F1000Res."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"210-8","DOI":"10.1177\/1040638713478608","article-title":"An investigation into beef calf mortality on five high-altitude ranches that selected sires with low pulmonary arterial pressures for over 20 years.","volume":"25","author":"J Neary","year":"2013","journal-title":"J Vet Diagn Invest."},{"key":"ref-11","first-page":"300","article-title":"Diseases of feedlot cattle","author":"R Jensen","year":"1979"},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1746-6148-4-25","article-title":"Prevalence of the prion protein gene E211K variant in U.S. cattle.","volume":"4","author":"M Heaton","year":"2008","journal-title":"BMC Vet Res."},{"key":"ref-13","article-title":"Calculation for the chi-square test: An interactive calculation tool for chi-square tests of goodness of fit and independence","author":"K Preacher","year":"2001"},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"153-7","DOI":"10.1007\/BF02295996","article-title":"Note on the sampling error of the difference between correlated proportions or percentages.","volume":"12","author":"Q McNemar","year":"1947","journal-title":"Psychometrika."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"99-110","DOI":"10.2147\/CLEP.S30816","article-title":"Matched case-control studies: a review of reported statistical methodology.","volume":"4","author":"D Niven","year":"2012","journal-title":"Clin Epidemiol."},{"key":"ref-16","article-title":"Table S1. Metadata and phased EPAS1 diplotypes for 102 case-control pairs","author":"M Heaton","year":"2019"},{"key":"ref-17","article-title":"Table S2. Summary of 36 possible EPAS1 diplotypes and their frequency in cases and controls","author":"M Heaton","year":"2019"},{"key":"ref-18","article-title":"Table S3. EPAS1 haplotype frequencies in cases and controls","author":"M Heaton","year":"2019"},{"key":"ref-19","article-title":"Table S4. EPAS1 risk factor scoring used in McNemar\u2019s Test with 102 matched pairs","author":"M Heaton","year":"2019"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/8-1189\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-1189\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-1189\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T13:45:20Z","timestamp":1569073520000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/8-1189\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,25]]},"references-count":19,"URL":"https:\/\/doi.org\/10.12688\/f1000research.19951.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.21898.r52931","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.21898.r52928","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.21898.r52928","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.21898.r52934","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.21898.r52931","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,25]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/8-1189\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.21898.r52928, Donagh P. Berry, Animal\u00a0and\u00a0Grassland Research and Innovation Centre, Teagasc, Fermoy, Ireland, 27 Aug 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-1189\/v1#referee-response-52928","order":0,"name":"referee-response-52928","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.21898.r52931, Emily L. Clark, The\u00a0Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK, 03 Sep 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-1189\/v1#referee-response-52931","order":1,"name":"referee-response-52931","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Funding for this research was provided by the USDA, ARS appropriated projects [5438-32000-033-00D] (MPH) and The University of Nebraska Great Plains Veterinary Educational Center [2162390003] (DMG, BLVL) and the Nebraska Beef Industry Endowment [2662390323001] (BLVL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}