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Externalizing behaviors, traits, and symptoms span a range of traditional psychiatric diagnostic categories. In this study, we sought to generate an algorithm that could reliably identify transdiagnostic childhood\u2010onset externalizing cases and controls within a university hospital electronic health record (EHR) database. Within the Vanderbilt University Medical Center (VUMC) EHR, our algorithm identified cases with a clinician\u2010validated positive predictive value of 90% and controls with a negative predictive value of 88%. In individuals of genetically defined European ancestry (CEU\u2010clustered; <jats:italic>N<\/jats:italic><jats:sub>case<\/jats:sub>\u2009=\u2009487, <jats:italic>N<\/jats:italic><jats:sub>control<\/jats:sub>\u2009=\u20095638), case status was significantly associated with psychiatric comorbidity and with elevated externalizing polygenic scores (OR: 1.20; 95% CI: 1.09\u20131.33; <jats:italic>p<\/jats:italic>\u2009=\u20091.14\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>; based on published genome\u2010wide association data). To test whether our cohort definitions could be applied to generate novel genetic insights, we examined rare (allele frequency &lt;\u20090.5%) copy number variation. An association (OR: 9.70; CI: 3.24\u201329.0) was identified in the CEU\u2010clustered cohort on chromosome 2 (chr2: 45,408,678\u201345,551,530; duplication), although the statistical strength of this association was modest (<jats:italic>p<\/jats:italic>\u2009=\u20090.052). We also examined the role of an externalizing burden score based on the number of externalizing diagnoses present in cases and found similar results to our case\u2013control analysis. This analysis identified several other statistically significant CNV region associations. This study provides a framework for identifying childhood externalizing case\u2013control cohorts within an EHR. Future work should validate this framework within other health systems. A broadly applicable algorithm, like this one, may allow for detection of rare outcomes or outcomes in populations historically excluded from genomic research through meta\u2010analysis of data across health care systems.<\/jats:p>","DOI":"10.1002\/ajmg.b.33020","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T09:49:04Z","timestamp":1735811344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Transdiagnostic Childhood Externalizing Pathology Within an Electronic Medical Records Database and Application to the Analysis of Rare Copy Number Variation"],"prefix":"10.1002","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6462-0866","authenticated-orcid":false,"given":"India A.","family":"Reddy","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lide","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Sanchez\u2010Roige","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Psychiatry University of California San Diego  La Jolla California USA"},{"name":"Institute for Genomic Medicine, University of California San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-7393","authenticated-orcid":false,"given":"Maria","family":"Niarchou","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas M.","family":"Ruderfer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea K.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1037\/h0093906"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2019_120"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2017.06.006"},{"key":"e_1_2_9_7_1","unstructured":"Child and Adolescent Health Measurement Initiative.2012.\u201cNational Survey of Children's Health. 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