{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T21:53:15Z","timestamp":1762033995228,"version":"3.37.3"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000092","name":"National Library of Medicine","doi-asserted-by":"publisher","award":["UL1 TR002243","R01-LM010685"],"award-info":[{"award-number":["UL1 TR002243","R01-LM010685"]}],"id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Knowledgebases are needed to clarify correlations observed in real-world electronic health record (EHR) data. We posit design principles, present a unifying framework, and report a test of concept.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>We structured a knowledge framework along 3 axes: condition of interest, knowledge source, and taxonomy. In our test of concept, we used hypertension as our condition of interest, literature and VanderbiltDDx knowledgebase as sources, and phecodes as our taxonomy. In a cohort of 832\u00a0566 deidentified EHRs, we modeled blood pressure and heart rate by sex and age, classified individuals by hypertensive status, and ran a Phenome-wide Association Study (PheWAS) for hypertension. We compared the correlations from PheWAS to the associations in our knowledgebase.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We produced PhecodeKbHtn: a knowledgebase comprising 167 hypertension-associated diseases, 15 of which were also negatively associated with blood pressure (pos+neg). Our hypertension PheWAS included 1914 phecodes, 129 of which were in the PhecodeKbHtn. Among the PheWAS association results, phecodes that were in PhecodeKbHtn had larger effect sizes compared with those phecodes not in the knowledgebase.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Each source contributed unique and additive associations. Models of blood pressure and heart rate by age and sex were consistent with prior cohort studies. All but 4 PheWAS positive and negative correlations for phecodes in PhecodeKbHtn may be explained by knowledgebase associations, hypertensive cardiac complications, or causes of hypertension independently associated with hypotension.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>It is feasible to assemble a knowledgebase that is compatible with EHR data to aid interpretation of clinical correlation research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jamia\/ocad078","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T08:43:06Z","timestamp":1683794586000},"page":"1257-1265","source":"Crossref","is-referenced-by-count":6,"title":["Knowledgebase strategies to aid interpretation of clinical correlation research"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5048-9540","authenticated-orcid":false,"given":"William W","family":"Stead","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center , Nashville, Tennessee, USA"},{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee, USA"}]},{"given":"Adam","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center , Nashville, Tennessee, USA"}]},{"given":"Nunzia B","family":"Giuse","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center , Nashville, Tennessee, USA"},{"name":"Center for Knowledge Management, Vanderbilt University Medical Center , Nashville, Tennessee, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-467X","authenticated-orcid":false,"given":"Taneya Y","family":"Koonce","sequence":"additional","affiliation":[{"name":"Center for Knowledge Management, Vanderbilt University Medical Center , Nashville, Tennessee, USA"}]},{"given":"Lisa","family":"Bastarache","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center , Nashville, Tennessee, USA"}]}],"member":"286","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"2023062008362891000_ocad078-B1","first-page":"212","article-title":"An analysis of diagnostic reasoning. I. The domains and disorders of clinical macrobiology","volume":"4","author":"Feinstein","year":"1973","journal-title":"Yale J Biol Med"},{"issue":"8058","key":"2023062008362891000_ocad078-B2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0140-6736(78)90496-8","article-title":"The effect of specialisation on the practice of medicine","volume":"1","author":"Godber","year":"1978","journal-title":"Lancet"},{"issue":"1","key":"2023062008362891000_ocad078-B3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1001\/jama.2021.20356","article-title":"Phenome-wide association studies","volume":"327","author":"Bastarache","year":"2022","journal-title":"JAMA"},{"key":"2023062008362891000_ocad078-B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-biodatasci-122320-112352","article-title":"Using phecodes for research with the electronic health record: from PheWAS to PheRS","volume":"4","author":"Bastarache","year":"2021","journal-title":"Annu Rev Biomed Data Sci"},{"issue":"1","key":"2023062008362891000_ocad078-B5","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1038\/s41467-018-05624-4","article-title":"A study paradigm integrating prospective epidemiologic cohorts and electronic health records to identify disease biomarkers","volume":"9","author":"Mosley","year":"2018","journal-title":"Nat Commun"},{"issue":"1","key":"2023062008362891000_ocad078-B6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1136\/amiajnl-2012-001145","article-title":"Next-generation phenotyping of electronic health records","volume":"20","author":"Hripcsak","year":"2013","journal-title":"J Am Med Inform Assoc"},{"issue":"2","key":"2023062008362891000_ocad078-B7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1136\/jamia.2000.0070135","article-title":"Integration and beyond: linking information from disparate sources and into workflow","volume":"7","author":"Stead","year":"2000","journal-title":"J Am Med Inform Assoc"},{"issue":"8","key":"2023062008362891000_ocad078-B8","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1056\/NEJM198208193070803","article-title":"Internist-1, an experimental computer-based diagnostic consultant for general internal medicine","volume":"307","author":"Miller","year":"1982","journal-title":"N Engl J Med"},{"author":"VDDx","key":"2023062008362891000_ocad078-B9"},{"issue":"3","key":"2023062008362891000_ocad078-B10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/bib\/bbl027","article-title":"Bio-ontologies: current trends and future directions","volume":"7","author":"Bodenreider","year":"2006","journal-title":"Brief Bioinform"},{"issue":"Web Server issue","key":"2023062008362891000_ocad078-B11","doi-asserted-by":"crossref","first-page":"W170","DOI":"10.1093\/nar\/gkp440","article-title":"BioPortal: ontologies and integrated data resources at the click of a mouse","volume":"37","author":"Noy","year":"2009","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"2023062008362891000_ocad078-B12","first-page":"489","article-title":"Knowledge graph refinement: a survey of approaches and evaluation methods","volume":"8","author":"Paulheim","year":"2016","journal-title":"SWJ"},{"issue":"2","key":"2023062008362891000_ocad078-B13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1145\/3329781.3332266","article-title":"Industry-scale knowledge graphs: lessons and challenges: five diverse technology companies show how it\u2019s done","volume":"17","author":"Noy","year":"2019","journal-title":"Queue"},{"issue":"4","key":"2023062008362891000_ocad078-B14","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2217\/pgs.10.15","article-title":"Pharmacogenomics and bioinformatics: PharmGKB","volume":"11","author":"Thorn","year":"2010","journal-title":"Pharmacogenomics"},{"issue":"4","key":"2023062008362891000_ocad078-B15","doi-asserted-by":"crossref","first-page":"e1417","DOI":"10.1002\/wsbm.1417","article-title":"PharmGKB: a worldwide resource for pharmacogenomic information","volume":"10","author":"Barbarino","year":"2018","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"author":"Phecode X. (Extended)","key":"2023062008362891000_ocad078-B16"},{"issue":"3","key":"2023062008362891000_ocad078-B17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0933-3657(93)90027-Z","article-title":"Consistency enforcement in medical knowledge base construction","volume":"5","author":"Giuse","year":"1993","journal-title":"Artif Intell Med"},{"key":"2023062008362891000_ocad078-B18","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jbi.2014.02.003","article-title":"Secondary use of clinical data: the Vanderbilt approach","volume":"52","author":"Danciu","year":"2014","journal-title":"J Biomed Inform"},{"issue":"19","key":"2023062008362891000_ocad078-B19","doi-asserted-by":"crossref","first-page":"e127","DOI":"10.1016\/j.jacc.2017.11.006","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"71","author":"Whelton","year":"2018","journal-title":"J Am Coll Cardiol"},{"issue":"260","key":"2023062008362891000_ocad078-B20","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/01621459.1952.10483441","article-title":"Use of ranks in one criterion variance analysis","volume":"47","author":"Kruskal","year":"1952","journal-title":"J Am Stat Assoc"},{"issue":"6","key":"2023062008362891000_ocad078-B21","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1161\/01.HYP.0000107251.49515.c2","article-title":"Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure","volume":"42","author":"Chobanian","year":"2003","journal-title":"Hypertension"},{"author":"Basile","key":"2023062008362891000_ocad078-B22"},{"issue":"8","key":"2023062008362891000_ocad078-B23","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1056\/NEJMcp071137","article-title":"Clinical practice. Isolated systolic hypertension in the elderly","volume":"357","author":"Chobanian","year":"2007","journal-title":"N Engl J Med"},{"author":"Bakris","key":"2023062008362891000_ocad078-B24"},{"issue":"Suppl 1","key":"2023062008362891000_ocad078-B25","first-page":"S80","article-title":"Treatment of hypertension in adults with diabetes","volume":"26","author":"Arauz-Pacheco","year":"2003","journal-title":"Diabetes Care"},{"key":"2023062008362891000_ocad078-B26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/00004872-199303000-00012","article-title":"Hypertension in Diabetes Study (HDS): I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications","volume":"11","year":"1993","journal-title":"J Hypertens"},{"issue":"2","key":"2023062008362891000_ocad078-B27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.amjhyper.2006.07.016","article-title":"Relationship of metabolic syndrome with pulse pressure in patients with essential hypertension","volume":"20","author":"Mul\u00e8","year":"2007","journal-title":"Am J Hypertens"},{"issue":"2","key":"2023062008362891000_ocad078-B28","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/j.ijcard.2013.03.080","article-title":"Restoration of blood pressure control with pacemaker implantation in a patient with bradycardia and resistant hypertension: a case report","volume":"167","author":"Ellims","year":"2013","journal-title":"Int J Cardiol"},{"author":"Vasan","key":"2023062008362891000_ocad078-B29"},{"author":"Rordorf","key":"2023062008362891000_ocad078-B30"},{"author":"Radhakrishnan","key":"2023062008362891000_ocad078-B31"},{"author":"Curhan","key":"2023062008362891000_ocad078-B32"},{"issue":"6","key":"2023062008362891000_ocad078-B33","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1046\/j.1523-1755.1999.00483.x","article-title":"Essential arterial hypertension and stone disease","volume":"55","author":"Borghi","year":"1999","journal-title":"Kidney Int"},{"author":"Mann","key":"2023062008362891000_ocad078-B34"},{"issue":"2","key":"2023062008362891000_ocad078-B35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.5049\/EBP.2015.13.2.41","article-title":"Hypertension in chronic glomerulonephritis","volume":"13","author":"Ihm","year":"2015","journal-title":"Electrolyte Blood Press"},{"issue":"2","key":"2023062008362891000_ocad078-B36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.14797\/mdcj-13-2-55","article-title":"Hypothyroidism and the heart","volume":"13","author":"Udovcic","year":"2017","journal-title":"Methodist Debakey Cardiovasc J"},{"issue":"9","key":"2023062008362891000_ocad078-B37","doi-asserted-by":"crossref","first-page":"993","DOI":"10.4330\/wjc.v6.i9.993","article-title":"Cardiac manifestations in systemic sclerosis","volume":"6","author":"Lambova","year":"2014","journal-title":"World J Cardiol"},{"issue":"12","key":"2023062008362891000_ocad078-B38","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/nbt.2749","article-title":"Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data","volume":"31","author":"Denny","year":"2013","journal-title":"Nat Biotechnol"},{"issue":"1","key":"2023062008362891000_ocad078-B39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ajhg.2014.06.002","article-title":"Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations","volume":"95","author":"Ganesh","year":"2014","journal-title":"Am J Hum Genet"},{"issue":"6","key":"2023062008362891000_ocad078-B40","doi-asserted-by":"crossref","first-page":"e044353","DOI":"10.1136\/bmjopen-2020-044353","article-title":"Longitudinal cohorts for harnessing the electronic health record for disease prediction in a US population","volume":"11","author":"Manemann","year":"2021","journal-title":"BMJ Open"},{"issue":"9","key":"2023062008362891000_ocad078-B41","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.2337\/dc20-2252","article-title":"Associations of systolic blood pressure and diastolic blood pressure with the incidence of coronary artery disease or cerebrovascular disease according to glucose status","volume":"44","author":"Yamada","year":"2021","journal-title":"Diabetes Care"},{"issue":"3","key":"2023062008362891000_ocad078-B42","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1161\/01.HYP.25.3.305","article-title":"Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988\u20131991","volume":"25","author":"Burt","year":"1995","journal-title":"Hypertension"},{"issue":"4","key":"2023062008362891000_ocad078-B43","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1097\/HJH.0000000000001920","article-title":"Ambulatory pulse pressure components: concept, determination and clinical relevance","volume":"37","author":"Gavish","year":"2019","journal-title":"J Hypertens"},{"issue":"3","key":"2023062008362891000_ocad078-B44","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1161\/01.HYP.37.3.869","article-title":"Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III","volume":"37","author":"Franklin","year":"2001","journal-title":"Hypertension"}],"container-title":["Journal of the American Medical Informatics Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jamia\/article-pdf\/30\/7\/1257\/50634303\/ocad078.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jamia\/article-pdf\/30\/7\/1257\/50634303\/ocad078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T08:38:38Z","timestamp":1687250318000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jamia\/article\/30\/7\/1257\/7159697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,5,10]]},"published-print":{"date-parts":[[2023,6,20]]}},"URL":"https:\/\/doi.org\/10.1093\/jamia\/ocad078","relation":{},"ISSN":["1067-5027","1527-974X"],"issn-type":[{"type":"print","value":"1067-5027"},{"type":"electronic","value":"1527-974X"}],"subject":[],"published-other":{"date-parts":[[2023,7,1]]},"published":{"date-parts":[[2023,5,10]]}}}