{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:27:36Z","timestamp":1790652456914,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["K01AA028292"],"award-info":[{"award-number":["K01AA028292"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Polygenic risk scores (PRS) represent an individual's summed genetic risk for a trait and can serve as biomarkers for disease. Less is known about the utility of PRS as a means to quantify genetic risk for substance use disorders (SUDs) than for many other traits. Nonetheless, the growth of large, electronic health record\u2010based biobanks makes it possible to evaluate the association of SUD PRS with other traits. We calculated PRS for smoking initiation, alcohol use disorder (AUD), and opioid use disorder (OUD) using summary statistics from the Million Veteran Program sample. We then tested the association of each PRS with its primary phenotype in the Penn Medicine BioBank (PMBB) using all available genotyped participants of African or European ancestry (AFR and EUR, respectively) (\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u200918,612). Finally, we conducted phenome\u2010wide association analyses (PheWAS) separately by ancestry and sex to test for associations across disease categories. Tobacco use disorder was the most common SUD in the PMBB, followed by AUD and OUD, consistent with the population prevalence of these disorders. All PRS were associated with their primary phenotype in both ancestry groups. PheWAS results yielded cross\u2010trait associations across multiple domains, including psychiatric disorders and medical conditions. SUD PRS were associated with their primary phenotypes; however, they are not yet predictive enough to be useful diagnostically. The cross\u2010trait associations of the SUD PRS are indicative of a broader genetic liability. Future work should extend findings to additional population groups and for other substances of abuse.\n                  <\/jats:p>","DOI":"10.1111\/adb.13099","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T04:46:16Z","timestamp":1633668376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic liability for substance use associated with medical comorbidities in electronic health records of African\u2010 and European\u2010ancestry individuals"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5137-9714","authenticated-orcid":false,"given":"Emily E.","family":"Hartwell","sequence":"first","affiliation":[{"name":"Mental Illness Research, Education and Clinical Center Corporal Michael J. Crescenz VA Medical Center  Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2253-839X","authenticated-orcid":false,"given":"Alison K.","family":"Merikangas","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5216-4670","authenticated-orcid":false,"given":"Shefali S.","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1208-1720","authenticated-orcid":false,"given":"Marylyn D.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Department of Genetics Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Institute for Biomedical Informatics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Regeneron Genetics Center","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0450","authenticated-orcid":false,"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Mental Illness Research, Education and Clinical Center Corporal Michael J. Crescenz VA Medical Center  Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8820-2659","authenticated-orcid":false,"given":"Rachel L.","family":"Kember","sequence":"additional","affiliation":[{"name":"Mental Illness Research, Education and Clinical Center Corporal Michael J. Crescenz VA Medical Center  Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Key substance use and mental health indicators in the United States: Results from the 2019 National Survey on Drug Use and Health (HHS Publication No. PEP20\u201007\u201001\u2010001, NSDUH Series H\u201055)","author":"Substance Abuse and Mental Health Services 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