{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:51:06Z","timestamp":1790272266561,"version":"4.1.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CHIR","award":["PJT-156306"],"award-info":[{"award-number":["PJT-156306"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Individuals with an Opioid Use Disorder (OUD) have increased rates of cannabis use in comparison to the general population. Research on the short- and long-term impacts of cannabis use in OUD patients has been inconclusive. A genetic component may contribute to cannabis cravings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Aims<\/jats:title>\n<jats:p>Identify genetic variants associated with cannabis use through Genome-wide Association Study (GWAS) methods and investigate a Polygenic Risk Score (PRS). In addition, we aim to identify any sex differences in effect size for genetic variants reaching or nearing genome-wide significance in the GWAS.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The study outcomes of interest were: regular cannabis use (yes\/no) (n = 2616), heaviness of cannabis use (n = 1293) and cannabis cravings (n = 836). Logistic and linear regressions were preformed, respectively, to test the association between genetic variants and each outcome, regular cannabis use and heaviness of cannabis use. GWAS summary statistics from a recent large meta-GWAS investigating cannabis use disorder were used to conduct PRS\u2019s. Findings are limited to a European ancestry sample.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>No genome-wide significant associations were found. Rs1813412 (chromosome 17) for regular cannabis use and rs62378502 (chromosome 5) for heaviness of cannabis use were approaching genome-wide significance. Both these SNPs were nominally significant (p&lt;0.05) within males and females, however sex did not modify the association. The PRS identified statistically significant association with cannabis cravings. The variance explained by all PRSs were less than 1.02x10<jats:sup>-2<\/jats:sup>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study provides promising results in understanding the genetic contribution to cannabis use in individuals living with OUD.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0289059","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T18:40:38Z","timestamp":1690396838000},"page":"e0289059","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetics of cannabis use in opioid use disorder: A genome-wide association and polygenic risk score study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5535-7432","authenticated-orcid":true,"given":"Alannah","family":"Hillmer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-5454","authenticated-orcid":true,"given":"Caroul","family":"Chawar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Lamri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Kapczinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-1851","authenticated-orcid":true,"given":"Luciano","family":"Minuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lehana","family":"Thabane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Paterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-9361","authenticated-orcid":true,"given":"Zainab","family":"Samaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"issue":"12","key":"pone.0289059.ref001","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S2215-0366(18)30337-7","article-title":"The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"5","author":"L. Degenhardt","year":"2018","journal-title":"The Lancet Psychiatry"},{"issue":"23","key":"pone.0289059.ref002","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1056\/NEJMra1402309","article-title":"Adverse Health Effects of Marijuana Use","volume":"370","author":"N. D. Volkow","year":"2014","journal-title":"N Engl J Med"},{"key":"pone.0289059.ref003"},{"issue":"2","key":"pone.0289059.ref004","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11065-012-9222-1","article-title":"Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences","volume":"23","author":"N. A. Crane","year":"2013","journal-title":"Neuropsychol. Rev."},{"issue":"2","key":"pone.0289059.ref005","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3390\/ijerph17020509","article-title":"Sex and gender interactions on the use and impact of recreational cannabis","volume":"17","author":"L. Greaves","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"pone.0289059.ref006","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.drugalcdep.2013.12.013","article-title":"Investigation of sex-dependent effects of cannabis in daily cannabis smokers","volume":"136","author":"Z. D. Cooper","year":"2014","journal-title":"Drug Alcohol Depend."},{"issue":"4","key":"pone.0289059.ref007","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s40473-018-0167-4","article-title":"Cannabis Use: Neurobiological, Behavioral, and Sex\/Gender Considerations","volume":"5","author":"A. B. Nia","year":"2018","journal-title":"Curr. Behav. Neuroscireports"},{"issue":"3","key":"pone.0289059.ref008","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1360-0443.2009.02831.x","article-title":"Genetic and environmental influences on cannabis use initiation and problematic use: a meta\u2010analysis of twin studies","volume":"105","author":"K. J. H. Verweij","year":"2010","journal-title":"Addiction"},{"issue":"1","key":"pone.0289059.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12920-021-01035-5","article-title":"Genetic basis of cannabis use: a systematic review","volume":"14","author":"A. Hillmer","year":"2021","journal-title":"BMC Med. Genomics"},{"issue":"5","key":"pone.0289059.ref010","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/mp.2017.200","article-title":"Genome-wide association study identifies a novel locus for cannabis dependence","volume":"23","author":"A. Agrawal","year":"2018","journal-title":"Mol. Psychiatry"},{"issue":"11","key":"pone.0289059.ref011","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1111\/add.14368","article-title":"Genome\u2010wide association meta\u2010analysis of age at first cannabis use.","volume":"113","author":"C. C. 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Neurosci."},{"issue":"12","key":"pone.0289059.ref014","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/S2215-0366(20)30339-4","article-title":"A large-scale genome-wide association study meta-analysis of cannabis use disorder","volume":"7","author":"E. C. Johnson","year":"2020","journal-title":"The Lancet Psychiatry"},{"issue":"1","key":"pone.0289059.ref015","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41380-020-00949-3","article-title":"Polysubstance use in the US opioid crisis","volume":"26","author":"W. M. Compton","year":"2021","journal-title":"Mol. Psychiatry"},{"issue":"3","key":"pone.0289059.ref016","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1521-0391.1993.tb00421.x","article-title":"Urine screening for marijuana among methadone\u2010maintained patients","volume":"2","author":"A. J. Saxon","year":"1993","journal-title":"Am. J. Addict."},{"issue":"4","key":"pone.0289059.ref017","doi-asserted-by":"crossref","first-page":"E665","DOI":"10.9778\/cmajo.20190026","article-title":"Cannabis use during methadone maintenance treatment for opioid use disorder: a systematic review and meta-analysis","volume":"7","author":"H. McBrien","year":"2019","journal-title":"C. open"},{"key":"pone.0289059.ref018","doi-asserted-by":"crossref","first-page":"101939","DOI":"10.1016\/j.cpr.2020.101939","article-title":"The relationship between cannabis use and patient outcomes in medication-based treatment of opioid use disorder: A systematic review","volume":"82","author":"S. Lake","year":"2020","journal-title":"Clin. Psychol. Rev."},{"issue":"1","key":"pone.0289059.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13073-020-00742-5","article-title":"Polygenic risk scores: from research tools to clinical instruments","volume":"12","author":"C. M. Lewis","year":"2020","journal-title":"Genome Med."},{"issue":"9","key":"pone.0289059.ref020","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41596-020-0353-1","article-title":"Tutorial: a guide to performing polygenic risk score analyses","volume":"15","author":"S. W. Choi","year":"2020","journal-title":"Nat. Protoc."},{"issue":"10","key":"pone.0289059.ref021","doi-asserted-by":"crossref","first-page":"e296","DOI":"10.1371\/journal.pmed.0040296","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"4","author":"E. Von Elm","year":"2007","journal-title":"PLoS Med."},{"issue":"12","key":"pone.0289059.ref022","doi-asserted-by":"crossref","DOI":"10.1046\/j.1360-0443.1998.9312185711.x","article-title":"The Maudsley Addiction Profile (MAP): a brief instrument for assessing treatment outcome","volume":"93","author":"J. Marsden","year":"2002","journal-title":"Addiction"},{"key":"pone.0289059.ref023","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"2013","edition":"5"},{"issue":"1\u20132","key":"pone.0289059.ref024","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.drugalcdep.2013.02.036","article-title":"Crosswalk between DSM-IV dependence and DSM-5 substance use disorders for opioids, cannabis, cocaine and alcohol","volume":"132","author":"W. M. Compton","year":"2013","journal-title":"Drug Alcohol Depend."},{"issue":"1","key":"pone.0289059.ref025","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13293-017-0130-1","article-title":"Association between cannabis use and methadone maintenance treatment outcomes: an investigation into sex differences","volume":"8","author":"L. Zielinski","year":"2017","journal-title":"Biol. Sex Differ."},{"issue":"1\u20133","key":"pone.0289059.ref026","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.drugalcdep.2008.12.010","article-title":"Reliability and validity of a short form of the Marijuana Craving Questionnaire","volume":"102","author":"S. J. Heishman","year":"2009","journal-title":"Drug Alcohol Depend."},{"issue":"1","key":"pone.0289059.ref027","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3109\/16066359.2011.569101","article-title":"A \u2018standard joint\u2019? The role of quantity in predicting cannabis-related problems","volume":"20","author":"C. Zeisser","year":"2012","journal-title":"Addict. Res. Theory"},{"issue":"1","key":"pone.0289059.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12954-021-00468-6","article-title":"The association between cannabis use and outcome in pharmacological treatment for opioid use disorder","volume":"18","author":"T. Rosic","year":"2021","journal-title":"Harm Reduct. J."},{"issue":"3","key":"pone.0289059.ref029","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"S. Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"issue":"1","key":"pone.0289059.ref030","doi-asserted-by":"crossref","first-page":"s13742","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"C. C. Chang","year":"2015","journal-title":"Gigascience"},{"key":"pone.0289059.ref031","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2013"},{"issue":"11","key":"pone.0289059.ref032","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/ng.3679","article-title":"Reference-based phasing using the Haplotype Reference Consortium panel","volume":"48","author":"P.-R. Loh","year":"2016","journal-title":"Nat. Genet."},{"issue":"10","key":"pone.0289059.ref033","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/ng.3656","article-title":"Next-generation genotype imputation service and methods","volume":"48","author":"S. Das","year":"2016","journal-title":"Nat. Genet."},{"key":"pone.0289059.ref034","unstructured":"TOPMed, \u201cTOPMed Imputation Server\u2014Reference Panels.\u201d [Online]. Available: https:\/\/topmedimpute.readthedocs.io\/en\/latest\/reference-panels.html."},{"issue":"7845","key":"pone.0289059.ref035","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","article-title":"Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program","volume":"590","author":"D. Taliun","year":"2021","journal-title":"Nature"},{"issue":"7","key":"pone.0289059.ref036","doi-asserted-by":"crossref","first-page":"giz082","DOI":"10.1093\/gigascience\/giz082","article-title":"PRSice-2: Polygenic Risk Score software for biobank-scale data","volume":"8","author":"S. W. Choi","year":"2019","journal-title":"Gigascience"},{"issue":"2","key":"pone.0289059.ref037","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/bib\/bbs038","article-title":"The UCSC genome browser and associated tools","volume":"14","author":"R. M. Kuhn","year":"2013","journal-title":"Brief. Bioinform."},{"issue":"18","key":"pone.0289059.ref038","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1093\/bioinformatics\/btab186","article-title":"LocusZoom. js: Interactive and embeddable visualization of genetic association study results","volume":"37","author":"A. P","year":"2021","journal-title":"Bioinformatics"},{"issue":"20","key":"pone.0289059.ref039","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1093\/bioinformatics\/btw373","article-title":"PhenoScanner: a database of human genotype\u2013phenotype associations","volume":"32","author":"J. R. Staley","year":"2016","journal-title":"Bioinformatics"},{"issue":"22","key":"pone.0289059.ref040","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: an expanded tool for searching human genotype\u2013phenotype associations","volume":"35","author":"M. A. Kamat","year":"2019","journal-title":"Bioinformatics"},{"issue":"D1","key":"pone.0289059.ref041","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019","volume":"47","author":"A. Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"pone.0289059.ref042","first-page":"D682","article-title":"Ensembl 2020","volume":"48","author":"A. D. Yates","year":"2020","journal-title":"Nucleic Acids Res."},{"issue":"8","key":"pone.0289059.ref043","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1101\/gr.9.8.677","article-title":"dbSNP\u2014database for single nucleotide polymorphisms and other classes of minor genetic variation","volume":"9","author":"S. T. Sherry","year":"1999","journal-title":"Genome Res."},{"issue":"4","key":"pone.0289059.ref044","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/add.14512","article-title":"Exploring the relationship between polygenic risk for cannabis use, peer cannabis use and the longitudinal course of cannabis involvement.","volume":"114","author":"E. C. Johnson","year":"2019","journal-title":"Addiction"},{"issue":"3","key":"pone.0289059.ref045","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/ajmg.b.32843","article-title":"Genomics and epigenomics of addiction","volume":"186","author":"R. Maldonado","year":"2021","journal-title":"Am. J. Med. GenetPart B Neuropsychiatr. Genet"},{"issue":"6","key":"pone.0289059.ref046","doi-asserted-by":"crossref","DOI":"10.1192\/bjo.2019.78","article-title":"The association between health conditions and cannabis use in patients with opioid use disorder receiving methadone maintenance treatment","volume":"5","author":"I. Shams","year":"2019","journal-title":"BJPsych open"},{"issue":"5","key":"pone.0289059.ref047","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/etm.2021.9976","article-title":"Understanding the genetics and neurobiological pathways behind addiction","volume":"21","author":"A. Popescu","year":"2021","journal-title":"Exp. Ther. Med."},{"issue":"3","key":"pone.0289059.ref048","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/alcalc\/agr030","article-title":"Personalized addiction treatment: how close are we?","volume":"46","author":"D. Oslin","year":"2011","journal-title":"Alcohol Alcohol."},{"key":"pone.0289059.ref049","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.neubiorev.2019.09.036","article-title":"How does cannabidiol (CBD) influence the acute effects of delta-9-tetrahydrocannabinol (THC) in humans? A systematic review","volume":"107","author":"A. M. Freeman","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"issue":"1","key":"pone.0289059.ref050","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/ije\/dyx206","article-title":"Collider scope: when selection bias can substantially influence observed associations","volume":"47","author":"M. R. Munaf\u00f2","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"pone.0289059.ref051","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2147\/NDT.S129480","article-title":"The impact of comorbid psychiatric disorders on methadone maintenance treatment in opioid use disorder: A prospective cohort study","volume":"13","author":"T. Rosic","year":"2017","journal-title":"Neuropsychiatr. Dis. 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