{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:26:36Z","timestamp":1768868796933,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,11]]},"group-title":"Addiction Medicine","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,11]]},"abstract":"<jats:title>Abstract<\/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-effective 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. Our approach comprises 1) alcohol-associated 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. Linking loci to genes from a genome-wide association study (GWAS) of problematic alcohol use identified 94 genes, which we expanded to 327 alcohol-related genes through network-based analyses. Across these analyses, 52 genes were linked to 195 FDA-approved drugs, including four already approved or used off-label 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-world effectiveness of baclofen using national EHR data from the United States Department of Veterans Affairs provided evidence that baclofen-exposed patients reduced alcohol consumption more than propensity-score-matched unexposed patients. This approach, which aligns genomic findings with real-world 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>","DOI":"10.64898\/2026.01.09.26343615","type":"posted-content","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T01:30:12Z","timestamp":1768181412000},"source":"Crossref","is-referenced-by-count":1,"title":["Bridging Genomics and Pharmacoepidemiology to Expand Treatment Options for Alcohol Use Disorder"],"prefix":"10.64898","author":[{"given":"Christopher T.","family":"Rentsch","sequence":"first","affiliation":[{"name":"Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, United States"},{"name":"Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha G.","family":"Malone","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, Bethesda, MD 20814, United States"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjian","family":"Shi","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, Bethesda, MD 20814, United States"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Setzer","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, Bethesda, MD 20814, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Piserchia","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, Bethesda, MD 20814, United States"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma L.","family":"Winterlind","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, Bethesda, MD 20814, United States"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, United States"},{"name":"Department of Psychology, University of Wyoming, Laramie, WY 82072, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, MD 21224, United States"},{"name":"Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Tazare","sequence":"additional","affiliation":[{"name":"Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy C.","family":"Justice","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, United States"},{"name":"Department of Health Policy and Management, Yale School of Public Health, New Haven, CT 06510, United States"},{"name":"VA Connecticut Healthcare System, West Haven, CT 06516, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Fiellin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, United States"},{"name":"Department of Health Policy and Management, Yale School of Public Health, New Haven, CT 06510, United States"},{"name":"Yale Program in Addiction Medicine, Yale School of Medicine, New Haven, CT 06510, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, MD 21224, United States"},{"name":"Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, RI 02903, United States"},{"name":"Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, United States"},{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Mental Illness Research, Education and Clinical Center, Crescenz VA Medical Center, Philadelphia, PA 19104, United States"},{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-561X","authenticated-orcid":false,"given":"Joshua C.","family":"Gray","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, Bethesda, MD 20814, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026011307250476000_2026.01.09.26343615v1.1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association . 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