{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:45:52Z","timestamp":1790685952131,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01 AA030041"],"award-info":[{"award-number":["R01 AA030041"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01 AA030056"],"award-info":[{"award-number":["R01 AA030056"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01 AA023733"],"award-info":[{"award-number":["R01 AA023733"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["P01 AA029545"],"award-info":[{"award-number":["P01 AA029545"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["HU0001\u201022\u20102\u20100066"],"award-info":[{"award-number":["HU0001\u201022\u20102\u20100066"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alcohol use disorder (AUD) is a chronic, relapsing condition and a major public health problem. However, few medications are approved to treat AUD, and those available show limited efficacy. Drug repurposing is a cost\u2010effective strategy to identify novel therapeutic uses for existing medications. Here, we describe a pipeline that integrates genetic and electronic health record (EHR) data to identify and evaluate drugs to be repurposed for treating AUD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Our approach comprises (1) alcohol\u2010associated gene identification and biological network generation; (2) mapping drugs to target proteins; (3) filtering promising repurposing candidates; and (4) an exemplar pharmacoepidemiologic analysis of the effect of an identified drug (i.e., baclofen) on alcohol consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Linking loci to genes from a genome\u2010wide association study (GWAS) of problematic alcohol use identified 94 genes, which we expanded to 327 alcohol\u2010related genes through network\u2010based analyses. Across these analyses, 52 genes were linked to 195 FDA\u2010approved drugs, including four already approved or used off\u2010label to treat AUD. After filtering for safety, relevance, and data availability, 26 candidate drugs, including baclofen, were selected for further evaluation. An evaluation of the real\u2010world effectiveness of baclofen using national EHR data from the United States Department of Veterans Affairs provided evidence that baclofen\u2010exposed patients reduced alcohol consumption more than propensity\u2010score\u2010matched unexposed patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This approach, which aligns genomic findings with real\u2010world clinical data, provides an efficient method for identifying promising drug repurposing candidates and prioritizing those that merit evaluation in randomized trials to ultimately advance pharmacotherapies for AUD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70247","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T15:00:51Z","timestamp":1773241251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bridging genomics and pharmacoepidemiology to expand treatment options for alcohol use disorder"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1408-7907","authenticated-orcid":false,"given":"Christopher T.","family":"Rentsch","sequence":"first","affiliation":[{"name":"Department of Medicine Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Faculty of Epidemiology and Population Health London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha G.","family":"Malone","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology Uniformed Services University of the Health Sciences  Bethesda Maryland USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-9822","authenticated-orcid":false,"given":"Mingjian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology Uniformed Services University of the Health Sciences  Bethesda Maryland USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Setzer","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology Uniformed Services University of the Health Sciences  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Piserchia","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology Uniformed Services University of the Health Sciences  Bethesda Maryland USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2104-1314","authenticated-orcid":false,"given":"Emma L.","family":"Winterlind","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology Uniformed Services University of the Health Sciences  Bethesda Maryland USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.  Bethesda Maryland USA"},{"name":"Department of Psychology University of Wyoming  Laramie Wyoming USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-4212","authenticated-orcid":false,"given":"Mehdi","family":"Farokhnia","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Baltimore Maryland USA"},{"name":"Department of Mental Health Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Tazare","sequence":"additional","affiliation":[{"name":"Faculty of Epidemiology and Population Health London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Justice","sequence":"additional","affiliation":[{"name":"Department of Medicine Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Health Policy and Management Yale School of Public Health  New Haven Connecticut USA"},{"name":"VA Connecticut Healthcare System  West Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-010X","authenticated-orcid":false,"given":"David A.","family":"Fiellin","sequence":"additional","affiliation":[{"name":"Department of Medicine Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Health Policy and Management Yale School of Public Health  New Haven Connecticut USA"},{"name":"Yale Program in Addiction Medicine Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-8754","authenticated-orcid":false,"given":"Lorenzo","family":"Leggio","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Baltimore Maryland USA"},{"name":"Department of Behavioral and Social Sciences, Center for Alcohol and Addiction Studies, School of Public Health Brown University  Providence Rhode Island USA"},{"name":"Division of Addiction Medicine, Department of Medicine, School of Medicine Johns Hopkins University  Baltimore Maryland USA"},{"name":"Department of Neuroscience Georgetown University Medical Center  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Mental Illness Research Education and Clinical Center, Crescenz VA Medical Center  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-561X","authenticated-orcid":false,"given":"Joshua C.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology Uniformed Services University of the Health Sciences  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"e_1_2_10_2_1","article-title":"Baclofen for alcohol use disorder","volume":"1","author":"Agabio R.","year":"2023","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(18)30303-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/00273171.2011.568786"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01327-9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01789-z"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj149"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107312"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.16.1789"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2024.100618"},{"key":"e_1_2_10_12_1","article-title":"Genomics of drug target prioritization for complex diseases","author":"Chen R.","year":"2025","journal-title":"Nature Reviews. Genetics"},{"key":"e_1_2_10_13_1","unstructured":"Congressional Budget Office. (2021)Research and development in the pharmaceutical industry. Congressional Budget Office Nonpartisan Analysis for the US Congress."},{"key":"e_1_2_10_14_1","volume-title":"Introduction to algorithms","author":"Cormen T.H.","year":"2001"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhealeco.2016.01.012"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1162\/rest.89.2.221"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.00047"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00751-0"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0287-y"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01736-y"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.71"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI188314"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.13.1977"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/02698811221149643"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI159103"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01478-5"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-4843-6"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2021.1271"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44220-023-00034-y"},{"key":"e_1_2_10_30_1","doi-asserted-by":"crossref","unstructured":"Ji C. Kerrebijn I. Arbabi K. Schipper M.&Wainberg M.(2025)Benchmarking genome\u2010wide association study causal gene prioritization for drug discovery. medRxiv 2025.09.23.25336370.","DOI":"10.1101\/2025.09.23.25336370"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008489"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1994.03950090052008"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14655"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.15118"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.15980"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1075"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1068162023020139"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1561\/0800000014"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152710790966614"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115443"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77847-9"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb05263.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1521-0391.2003.tb00543.x"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.19761"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1075"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2430-1"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07316-0"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00945-5"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1046"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-015-9860-5"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr352"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.7326\/M21-4011"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13953"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agz082"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05477-4"},{"key":"e_1_2_10_56_1","unstructured":"Substance Abuse and Mental Health Services Administration. (2024)Center for Behavioral Health Statistics and Quality. 2022 National Survey on Drug Use and Health. Table\u00a05.9B\u2014Alcohol use disorder in past year: among people aged 12 or older; by age group and demographic characteristics percentages 2022 and 2023. Center for Behavioral Health Statistics and Quality Substance Abuse and Mental Health Services Administration."},{"key":"e_1_2_10_57_1","unstructured":"U.S. Department of Veterans Affairs. (2025)About the department. US Department of Veterans Affairs.https:\/\/department.va.gov\/about\/"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.266"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3721-16.2017"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbad527"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.4221"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax4043"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1166"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1004"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02653-5"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-022-00617-6"}],"container-title":["Alcohol, Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70247","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acer.70247","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70247","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:58:01Z","timestamp":1785520681000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.70247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":65,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/acer.70247"],"URL":"https:\/\/doi.org\/10.1111\/acer.70247","archive":["Portico"],"relation":{},"ISSN":["2993-7175","2993-7175"],"issn-type":[{"value":"2993-7175","type":"print"},{"value":"2993-7175","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-08-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70247"}}