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Med."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S003329172610470X_sec1\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Persons with substance use disorders (SUD) often suffer from additional comorbidities. Researchers have explored this overlap via phenome-wide association studies (PheWASs). However, PheWASs are largely cross-sectional, limiting our understanding of whether diagnoses predate the development of an SUD. We characterize whether polygenic scores (PGSs) are associated with time to comorbid diagnoses in electronic health records (EHR) after the first documented SUD diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S003329172610470X_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using data from All of Us (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0393,596), we explored: (1) whether social determinants of health (SDoHs) are associated with lifetime risk of SUD (\n                      <jats:italic>N<\/jats:italic>\n                      cases\u00a0=\u00a042,568) and (2) within a subset those with a diagnosed SUD and available genetic data SUD (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a021,357), whether PGS for alcohol use disorders, cannabis use disorders, depression, externalizing, posttraumatic stress disorder, and schizophrenia were associated with subsequent diagnoses via a phenome-wide survival analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S003329172610470X_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Multiple SDoHs were associated with lifetime SUD diagnosis, with annual household income having the largest overall associations (e.g. &lt;$10\u00a0K annually vs $100\u00a0K\u2013$150\u00a0K annually: OR\u00a0=\u00a04.18; 95% CI\u00a0=\u00a03.92, 4.45). There were 86 phenome-wide significant PGS associations with subsequent diagnoses across various bodily systems. PGSs for alcohol use disorders, posttraumatic stress disorder, and schizophrenia were each associated with time to their respective diagnoses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S003329172610470X_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Social determinants, especially those related to income, have profound associations with lifetime SUD risk. Additionally, PGSs for psychiatric conditions are associated with multiple post-SUD diagnoses within those with a SUD, suggesting PGS may capture information beyond lifetime risk, including timing and severity of comorbidities related to SUD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s003329172610470x","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:17:57Z","timestamp":1780291077000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":1,"title":["Polygenic risk factors for comorbid diagnoses in individuals with substance use disorders: A phenome-wide survival analysis"],"prefix":"10.1017","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-657X","authenticated-orcid":false,"given":"Peter B.","family":"Barr","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/03s5r4e84","id-type":"ROR","asserted-by":"publisher"}],"name":"VA New York Harbor Healthcare System"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6440-2445","authenticated-orcid":false,"given":"Z\u00f6e E.","family":"Neale","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/03s5r4e84","id-type":"ROR","asserted-by":"publisher"}],"name":"VA New York Harbor Healthcare System"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim B.","family":"Bigdeli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/03s5r4e84","id-type":"ROR","asserted-by":"publisher"}],"name":"VA New York Harbor Healthcare System"},{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Chatzinakos","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"},{"id":[{"id":"https:\/\/ror.org\/0041qmd21","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Downstate Health Sciences University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D.","family":"Harvey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dgjyy92","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Miami Miller School of Medicine"},{"id":[{"id":"https:\/\/ror.org\/01rjj8a34","id-type":"ROR","asserted-by":"publisher"}],"name":"Research Service, Bruce W. 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