{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:34:35Z","timestamp":1780569275361,"version":"3.54.1"},"reference-count":60,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:sec id=\"ab-yoi230084-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans\u2019 health, such as suicide-related behaviors and substance use disorders (SUDs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi230084-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi230084-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed. Lastly, to adjust for unmeasured confounders, a within-family analysis of significant associations from the main PheWAS was performed in full siblings (European ancestries only). This study included the electronic health record data from US veterans from VA health care centers enrolled in MVP. Analyses took place from February 2022 to August 2023 covering a period from October 1999 to January 2020.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi230084-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>PGSs for EXT, depression, schizophrenia, and suicide attempt.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi230084-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>\n                      Phecodes for diagnoses derived from the\n                      <jats:italic>International Statistical Classification of Diseases<\/jats:italic>\n                      ,\n                      <jats:italic>Ninth<\/jats:italic>\n                      and\n                      <jats:italic>Tenth Revisions<\/jats:italic>\n                      ,\n                      <jats:italic>Clinical Modification<\/jats:italic>\n                      , codes from electronic health records.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi230084-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Within the MVP (560\u202f824 patients; mean [SD] age,\u200967.9 [14.3] years; 512\u202f593 male [91.4%]), the EXT PGS was associated with 619 outcomes, of which 188 were independent of risk for comorbid problems or PGSs (from odds ratio [OR],\u20091.02; 95% CI,\u20091.01-1.03 for overweight\/obesity to OR,\u20091.44; 95% CI,\u20091.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant in the African results and 26 (4.5%) were significant in the Hispanic or Latin American results. Within-family analyses uncovered robust associations between EXT PGS and consequences of SUDs, including liver disease, chronic airway obstruction, and viral hepatitis C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-yoi230084-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Results of this cohort study suggest a shared polygenic basis of EXT disorders, independent of risk for other psychiatric problems. In addition, this study found associations between EXT PGS and diagnoses related to SUDs and their sequelae. Overall, this study highlighted the potential negative consequences of EXT disorders for health and functioning in the US veteran population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2023.4141","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T11:03:21Z","timestamp":1699441401000},"page":"188","source":"Crossref","is-referenced-by-count":7,"title":["Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort"],"prefix":"10.1001","volume":"81","author":[{"given":"Peter B.","family":"Barr","sequence":"first","affiliation":[{"name":"VA New York Harbor Healthcare System, Brooklyn"},{"name":"Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, New York"},{"name":"Institute for Genomics in Health, SUNY Downstate Health Sciences University, Brooklyn, New York"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim B.","family":"Bigdeli","sequence":"additional","affiliation":[{"name":"VA New York Harbor Healthcare System, Brooklyn"},{"name":"Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, New York"},{"name":"Institute for Genomics in Health, SUNY Downstate Health Sciences University, Brooklyn, New York"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn L.","family":"Meyers","sequence":"additional","affiliation":[{"name":"VA New York Harbor Healthcare System, Brooklyn"},{"name":"Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, New York"},{"name":"Institute for Genomics in Health, SUNY Downstate Health Sciences University, Brooklyn, New York"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roseann E.","family":"Peterson","sequence":"additional","affiliation":[{"name":"VA New York Harbor Healthcare System, Brooklyn"},{"name":"Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, New York"},{"name":"Institute for Genomics in Health, SUNY Downstate Health Sciences University, Brooklyn, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sanchez-Roige","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California San Diego, La Jolla"},{"name":"Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis T.","family":"Mallard","sequence":"additional","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"Dick","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey"},{"name":"Rutgers Addiction Research Center, Rutgers University, Piscataway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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