{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T15:53:56Z","timestamp":1778428436295,"version":"3.51.4"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA039841"],"award-info":[{"award-number":["DA039841"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99 DA043573"],"award-info":[{"award-number":["K99 DA043573"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA034196"],"award-info":[{"award-number":["P30 CA034196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 DA043809"],"award-info":[{"award-number":["U01 DA043809"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM OD 023222"],"award-info":[{"award-number":["UM OD 023222"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA048890"],"award-info":[{"award-number":["R01 DA048890"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Substance use disorders are heritable disorders characterized by compulsive drug use, the biological mechanisms for which remain largely unknown. Genetic correlations reveal that predisposing drug\u2010na\u00efve phenotypes, including anxiety, depression, novelty preference and sensation seeking, are predictive of drug\u2010use phenotypes, thereby implicating shared genetic mechanisms. High\u2010throughput behavioral screening in knockout (KO) mice allows efficient discovery of the function of genes. We used this strategy in two rounds of candidate prioritization in which we identified 33 drug\u2010use candidate genes based upon predisposing drug\u2010na\u00efve phenotypes and ultimately validated the perturbation of 22 genes as causal drivers of substance intake. We selected 19\/221 KO strains (8.5%) that had a difference from control on at least one drug\u2010na\u00efve predictive behavioral phenotype and determined that 15\/19 (~80%) affected the consumption or preference for alcohol, methamphetamine or both. No mutant exhibited a difference in nicotine consumption or preference which was possibly confounded with saccharin. In the second round of prioritization, we employed a multivariate approach to identify outliers and performed validation using methamphetamine two\u2010bottle choice and ethanol drinking\u2010in\u2010the\u2010dark protocols. We identified 15\/401 KO strains (3.7%, which included one gene from the first cohort) that differed most from controls for the predisposing phenotypes. 8 of 15 gene deletions (53%) affected intake or preference for alcohol, methamphetamine or both. Using multivariate and bioinformatic analyses, we observed multiple relations between predisposing behaviors and drug intake, revealing many distinct biobehavioral processes underlying these relationships. The set of mouse models identified in this study can be used to characterize these addiction\u2010related processes further.<\/jats:p>","DOI":"10.1111\/gbb.12875","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T09:12:08Z","timestamp":1704186728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery and validation of genes driving drug\u2010intake and related behavioral traits in mice"],"prefix":"10.1111","volume":"23","author":[{"given":"Tyler A.","family":"Roy","sequence":"first","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5013-1234","authenticated-orcid":false,"given":"Jason A.","family":"Bubier","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Price E.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Joan C Edwards School of Medicine Marshall University Huntington West Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troy D.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliet","family":"Ndukum","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Clark","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey J.","family":"Sukoff Rizzo","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"},{"name":"School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Crabbe","sequence":"additional","affiliation":[{"name":"VA Portland Health Care System Oregon Health &amp; Science University Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Denegre","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Svenson","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Braun","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6643-7465","authenticated-orcid":false,"given":"Vivek","family":"Kumar","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Murray","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline K.","family":"White","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek M.","family":"Philip","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elissa J.","family":"Chesler","sequence":"additional","affiliation":[{"name":"Center for Addiction Biology The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2012.03.010"},{"key":"e_1_2_9_3_1","volume-title":"Drugs, Brains, and Behavior: the Science of Addiction National Institute on Drug Abuse Website","author":"NIDA","year":"2018"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00014.2018"},{"key":"e_1_2_9_5_1","first-page":"1","volume-title":"Key Substance Use and Mental Health Indicators in the United States: Results from the 2015 National Survey on Drug Use and Health","author":"Administration SAaMHS","year":"2018"},{"key":"e_1_2_9_6_1","unstructured":"Services USDoHaH.The National Survey on Drug Use and Health Report 2018: 1\u201358."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209252"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)00104-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00125.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3901"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0904-921"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.018"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-012-9422-2"},{"key":"e_1_2_9_14_1","first-page":"1","article-title":"Impulsivity and sensation seeking in alcohol abusing patients with schizophrenia","volume":"1","author":"Dervaux A","year":"2010","journal-title":"Front Psych"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0b013e3283523dcc"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.186.3.190"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2016.1183020"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01274-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509724103"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0111-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-014-3737-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2009.00540.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.07.010"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2012.00780.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131274"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.85"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2017.04.012"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00442824"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.117.4.716"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00421184"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addicn.2022.100045"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-017-5021-5"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2004.00101.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/wics.101"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","unstructured":"KassambaraA MundtF.Factoextra: Extract and Visualize the Results of Multivariate Data Analyses.2017.","DOI":"10.32614\/CRAN.package.factoextra"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac970763d"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900911"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2007.12.006"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2004.10.007"},{"key":"e_1_2_9_40_1","article-title":"\"Drinking in the dark\" (DID): a simple mouse model of binge\u2010like alcohol intake","volume":"68","author":"Thiele TE","year":"2015","journal-title":"Curr Protoc Neurosci"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2013.08.005"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2014.06.004"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2017.10.034"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000164544.45746.A7"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1252-0"},{"key":"e_1_2_9_46_1","first-page":"63","volume-title":"Selected Methods of Emergency Toxicology","author":"Gadsden R","year":"1986"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1329"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11192-016-2119-7"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1055"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg112"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky962"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1070"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12021-008-9024-z"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1120"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0309-1740(00)00050-4"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meatsci.2004.01.002"},{"key":"e_1_2_9_60_1","doi-asserted-by":"crossref","unstructured":"MitraA DeatsSP DicksonPE et al.Tmod2is a regulator of cocaine responses through control of striatal and cortical excitability and drug\u2010induced plasticity.bioRxiv.2019. doi:10.1101\/648295","DOI":"10.1101\/648295"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1037\/1064-1297.13.4.367"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(94)00382-F"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(93)90046-Q"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1635"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1583"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00993"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2536"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46472"},{"key":"e_1_2_9_69_1","first-page":"1563","article-title":"Immunology of IL\u201012: an update on functional activities and implications for disease","volume":"19","author":"Ullrich KA","year":"2020","journal-title":"EXCLI J"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.04.018"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02255.x"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-009-9239-9"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13923"}],"container-title":["Genes, Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gbb.12875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T02:12:02Z","timestamp":1730945522000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gbb.12875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,2]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/gbb.12875"],"URL":"https:\/\/doi.org\/10.1111\/gbb.12875","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.09.548280","asserted-by":"object"}]},"ISSN":["1601-1848","1601-183X"],"issn-type":[{"value":"1601-1848","type":"print"},{"value":"1601-183X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,2]]},"assertion":[{"value":"2023-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12875"}}