{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:17:47Z","timestamp":1788499067250,"version":"build-2803163510"},"reference-count":85,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Chair in Cardiovascular Risk Reduction (CIRRCE, Badajoz, Spain) at the University of Extremadura"},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014181","name":"Regional Government of Extremadura","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014181","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01df4mv68","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014181","name":"Ministry of Finance","doi-asserted-by":"publisher","award":["GR24027"],"award-info":[{"award-number":["GR24027"]}],"id":[{"id":"10.13039\/501100014181","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Tobacco use disorder (TUD) is a complex multifactorial condition resulting from the interplay between nicotine-induced neurobiological adaptations, behavioral and learning processes, environmental influences, and individual genetic susceptibility. Genetic research has progressively evolved from twin and family studies through candidate-gene approaches to large-scale genome-wide association studies (GWAS), substantially improving our understanding of the genetic architecture of tobacco use and nicotine dependence. This review summarizes the current evidence on the genetic basis of TUD, with particular emphasis on major biological pathways. We also discuss the limitations of early candidate-gene studies and the paradigm shift introduced by large GWAS and meta-analyses, and polygenic risk scores, which indicate that tobacco use and nicotine dependence have a highly polygenic and pleiotropic architecture. Finally, we review the potential clinical applications of genetic information in smoking-cessation treatment, while highlighting current limitations in clinical translation. In the future, it is clear that a multidisciplinary approach\u2014combining genetics, clinical practice, and social sciences\u2014will be necessary to transform tobacco use management into a precision-based model and reduce its impact on public health.<\/jats:p>","DOI":"10.3390\/genes17091064","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:56:01Z","timestamp":1788339361000},"page":"1064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Basis of Tobacco Use Disorder"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-9767","authenticated-orcid":false,"given":"Guillermo","family":"Gervasini","sequence":"first","affiliation":[{"name":"Department of Medical-Surgical Therapeutics, Faculty of Medicine, University of Extremadura, 06006 Badajoz, Spain"},{"name":"Institute of Molecular Pathology Biomarkers, University of Extremadura, 06006 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","unstructured":"WHO (2026, July 03). Tobacco and Nicotine. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/tobacco."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.21037\/jtd.2020.02.47","article-title":"Cardiovascular risk of smoking and benefits of smoking cessation","volume":"12","author":"Gallucci","year":"2020","journal-title":"J. Thorac. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nrn2849","article-title":"Nicotine addiction and nicotinic receptors: Lessons from genetically modified mice","volume":"11","author":"Changeux","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0893-133X(99)00146-3","article-title":"Nicotinic receptors in the brain. Links between molecular biology and behavior","volume":"22","author":"Picciotto","year":"2000","journal-title":"Neuropsychopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"301","DOI":"10.4103\/0019-5545.74303","article-title":"Biological basis of tobacco addiction: Implications for smoking-cessation treatment","volume":"52","author":"Jiloha","year":"2010","journal-title":"Indian J. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"(2008). Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am. J. Prev. Med., 35, 158\u2013176.","DOI":"10.1016\/j.amepre.2008.04.009"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40429-013-0006-3","article-title":"Genetics and smoking","volume":"1","author":"Loukola","year":"2014","journal-title":"Curr. Addict. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJM199209173271201","article-title":"Genetic influence on smoking\u2014A study of male twins","volume":"327","author":"Carmelli","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0899-3289(93)90065-J","article-title":"Genetic contribution to risk of smoking initiation: Comparisons across birth cohorts and across cultures","volume":"5","author":"Heath","year":"1993","journal-title":"J. Subst. Abus."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0306-4603(93)90005-T","article-title":"Genetic models for the natural history of smoking: Evidence for a genetic influence on smoking persistence","volume":"18","author":"Heath","year":"1993","journal-title":"Addict. Behav."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/add.12449","article-title":"Initial reactions to tobacco and cannabis smoking: A twin study","volume":"109","author":"Agrawal","year":"2014","journal-title":"Addiction"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1046\/j.1360-0443.2003.00295.x","article-title":"A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins","volume":"98","author":"Li","year":"2003","journal-title":"Addiction"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nature06846","article-title":"A variant associated with nicotine dependence, lung cancer and peripheral arterial disease","volume":"452","author":"Thorgeirsson","year":"2008","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Caporaso, N., Gu, F., Chatterjee, N., Sheng-Chih, J., Yu, K., Yeager, M., Chen, C., Jacobs, K., Wheeler, W., and Landi, M.T. (2009). Genome-wide and candidate gene association study of cigarette smoking behaviors. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004653"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/ng.572","article-title":"Meta-analysis and imputation refines the association of 15q25 with smoking quantity","volume":"42","author":"Liu","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tobacco and Genetics Consortium (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat. Genet., 42, 441\u2013447.","DOI":"10.1038\/ng.571"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e119","DOI":"10.1038\/tp.2012.41","article-title":"Genome-wide meta-analyses of smoking behaviors in African Americans","volume":"2","author":"David","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1007\/s00439-011-1102-x","article-title":"Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence","volume":"131","author":"Yoon","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41562-019-0557-y","article-title":"GWAS of smoking behaviour in 165,436 Japanese people reveals seven new loci and shared genetic architecture","volume":"3","author":"Matoba","year":"2019","journal-title":"Nat. Hum. Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s10519-005-9012-0","article-title":"Genome-wide linkage scan to identify Loci for age at first cigarette in Dutch sibling pairs","volume":"36","author":"Vink","year":"2006","journal-title":"Behav. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1038\/s41380-018-0313-0","article-title":"Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci","volume":"25","author":"Erzurumluoglu","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5302","DOI":"10.1038\/s41467-020-18489-3","article-title":"Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals","volume":"11","author":"Xu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/s41586-022-05477-4","article-title":"Genetic diversity fuels gene discovery for tobacco and alcohol use","volume":"612","author":"Saunders","year":"2022","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10519-004-1327-8","article-title":"Heritability of smoking initiation and nicotine dependence","volume":"35","author":"Vink","year":"2005","journal-title":"Behav. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1111\/add.15450","article-title":"Genetic architecture of four smoking behaviors using partitioned SNP heritability","volume":"116","author":"Evans","year":"2021","journal-title":"Addiction"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1111\/add.15697","article-title":"Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood","volume":"117","author":"Deak","year":"2022","journal-title":"Addiction"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1093\/ntr\/ntab100","article-title":"Studying the Utility of Using Genetics to Predict Smoking-Related Outcomes in a Population-Based Study and a Selected Cohort","volume":"23","author":"Bray","year":"2021","journal-title":"Nicotine Tob. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1093\/ntr\/ntab105","article-title":"Multi-Polygenic Analysis of Nicotine Dependence in Individuals of European Ancestry","volume":"23","author":"Risner","year":"2021","journal-title":"Nicotine Tob. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.tins.2016.10.005","article-title":"The CHRNA5-A3-B4 Gene Cluster and Smoking: From Discovery to Therapeutics","volume":"39","author":"Lassi","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/sj.mp.4001774","article-title":"Why do young women smoke? I. Direct and interactive effects of environment, psychological characteristics and nicotinic cholinergic receptor genes","volume":"11","author":"Greenbaum","year":"2006","journal-title":"Mol. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/mp.2016.13","article-title":"A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences","volume":"21","author":"Thorgeirsson","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/14622200410001734030","article-title":"The genetic basis for smoking behavior: A systematic review and meta-analysis","volume":"6","author":"Munafo","year":"2004","journal-title":"Nicotine Tob. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/sj.mp.4000532","article-title":"Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers","volume":"4","author":"Jonsson","year":"1999","journal-title":"Mol. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e686","DOI":"10.1038\/tp.2015.176","article-title":"The significant association of Taq1A genotypes in DRD2\/ANKK1 with smoking cessation in a large-scale meta-analysis of Caucasian populations","volume":"5","author":"Ma","year":"2015","journal-title":"Transl. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/FPC.0000000000000403","article-title":"The effect of SLC6A3 variable number of tandem repeats and methylation levels on individual susceptibility to start tobacco smoking and on the ability of smokers to quit smoking","volume":"30","author":"Tiili","year":"2020","journal-title":"Pharmacogenet. Genom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/00008571-200008000-00001","article-title":"Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers","volume":"10","author":"McKinney","year":"2000","journal-title":"Pharmacogenetics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/ajmg.b.30004","article-title":"Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction","volume":"128B","author":"Chatkin","year":"2004","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.clpt.2004.02.011","article-title":"Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity","volume":"76","author":"Dempsey","year":"2004","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/cpt.2345","article-title":"The Role of Pharmacogenetics in Smoking","volume":"110","author":"Tyndale","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/sj.mp.4001794","article-title":"Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy","volume":"11","author":"Malaiyandi","year":"2006","journal-title":"Mol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tips.2016.09.006","article-title":"Pharmacogenetic Optimization of Smoking Cessation Treatment","volume":"38","author":"Chenoweth","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1038\/s41380-020-0702-z","article-title":"Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent","volume":"26","author":"Buchwald","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/hmg\/ddt432","article-title":"Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms","volume":"23","author":"Bloom","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1360-0443.2008.02445.x","article-title":"Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerstrom Test for Nicotine Dependence","volume":"104","author":"Agrawal","year":"2009","journal-title":"Addiction"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1124\/pr.116.012484","article-title":"The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis","volume":"68","author":"Scofield","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"467","DOI":"10.12740\/PP\/171620","article-title":"The rs4354668 polymorphism in the SLC1A2 gene for the EAAT2 glutamate transporter is associated with an increased risk of harmful drug use\u2014An exploratory study on a university student population","volume":"58","author":"Dawidowski","year":"2024","journal-title":"Psychiatr. Pol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ajhg.2009.02.001","article-title":"Genome-wide association study of smoking initiation and current smoking","volume":"84","author":"Vink","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1158\/1055-9965.EPI-22-0868","article-title":"Impact of Genetic Variants in the Nicotine Metabolism Pathway on Nicotine Metabolite Levels in Smokers","volume":"32","author":"Watson","year":"2023","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e00651","DOI":"10.1002\/brb3.651","article-title":"Targeted sequencing identifies genetic polymorphisms of flavin-containing monooxygenase genes contributing to susceptibility of nicotine dependence in European American and African American","volume":"7","author":"Zhang","year":"2017","journal-title":"Brain Behav."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20092","DOI":"10.1038\/srep20092","article-title":"Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2","volume":"6","author":"Ware","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/mp.2013.72","article-title":"Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample","volume":"19","author":"Loukola","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zeilinger, S., Kuhnel, B., Klopp, N., Baurecht, H., Kleinschmidt, A., Gieger, C., Weidinger, S., Lattka, E., Adamski, J., and Peters, A. (2013). Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063812"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1056\/NEJM199907013410106","article-title":"Shattuck lecture\u2014Medical and societal consequences of the Human Genome Project","volume":"341","author":"Collins","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1038\/s41591-022-01767-6","article-title":"Development of a clinical polygenic risk score assay and reporting workflow","volume":"28","author":"Hao","year":"2022","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"112415","DOI":"10.1016\/j.drugalcdep.2024.112415","article-title":"Polygenic risk scores for nicotine use and family history of smoking are associated with smoking behaviour","volume":"263","author":"Foo","year":"2024","journal-title":"Drug Alcohol. Depend."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1161\/STROKEAHA.120.031622","article-title":"Genetically Determined Smoking Behavior and Risk of Nontraumatic Subarachnoid Hemorrhage","volume":"52","author":"Acosta","year":"2021","journal-title":"Stroke"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41537-020-00126-z","article-title":"Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia","volume":"6","author":"Ohi","year":"2020","journal-title":"npj Schizophr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/carcin\/bgab018","article-title":"Incorporating both genetic and tobacco smoking data to identify high-risk smokers for lung cancer screening","volume":"42","author":"Jia","year":"2021","journal-title":"Carcinogenesis"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1478-7547-8-18","article-title":"Within a smoking-cessation program, what impact does genetic information on lung cancer need to have to demonstrate cost-effectiveness?","volume":"8","author":"Gordon","year":"2010","journal-title":"Cost. Eff. Resour. Alloc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1093\/ntr\/ntac043","article-title":"The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence from Two Treatment Trials","volume":"24","author":"Bray","year":"2022","journal-title":"Nicotine Tob. Res."},{"key":"ref_61","first-page":"435","article-title":"Evaluation of a Novel Difficulty of Smoking Cessation Phenotype Based on Number of Quit Attempts","volume":"19","author":"Stevens","year":"2017","journal-title":"Nicotine Tob. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S398","DOI":"10.1016\/j.amepre.2007.09.006","article-title":"Genetics and smoking cessation improving outcomes in smokers at risk","volume":"33","author":"Lerman","year":"2007","journal-title":"Am. J. Prev. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/cpt.3210","article-title":"Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline","volume":"115","author":"Chenoweth","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1093\/ntr\/ntu161","article-title":"Organic cation transporter variation and response to smoking cessation therapies","volume":"16","author":"Bergen","year":"2014","journal-title":"Nicotine Tob. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/npp.2011.232","article-title":"Smoking cessation pharmacogenetics: Analysis of varenicline and bupropion in placebo-controlled clinical trials","volume":"37","author":"King","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/cpt.1971","article-title":"Genetic Variant in CHRNA5 and Response to Varenicline and Combination Nicotine Replacement in a Randomized Placebo-Controlled Trial","volume":"108","author":"Chen","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1093\/ntr\/ntac268","article-title":"Influence of CYP2A6 Genetic Variation, Nicotine Dependence Severity, and Treatment on Smoking Cessation Success","volume":"25","author":"Chenoweth","year":"2023","journal-title":"Nicotine Tob. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00228-019-02731-z","article-title":"Cytochrome P450 2A6 and 2B6 polymorphisms and smoking cessation success in patients treated with varenicline","volume":"75","author":"Tomaz","year":"2019","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/clpt.2012.186","article-title":"CYP2B6 and bupropion\u2019s smoking-cessation pharmacology: The role of hydroxybupropion","volume":"92","author":"Zhu","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1093\/hmg\/ddn181","article-title":"Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation","volume":"17","author":"Conti","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1080\/14622200701382033","article-title":"Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation","volume":"9","author":"David","year":"2007","journal-title":"Nicotine Tob. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1111\/add.12325","article-title":"Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: Results from two randomized clinical trials of bupropion","volume":"108","author":"David","year":"2013","journal-title":"Addiction"},{"key":"ref_73","first-page":"33","article-title":"Are serotonergic system genes associated to smoking cessation therapy success in addition to CYP2A6?","volume":"47","author":"Verde","year":"2014","journal-title":"Pharmacopsychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/npp.2014.269","article-title":"Expression of the 5-HT1A serotonin receptor in the hippocampus is required for social stress resilience and the antidepressant-like effects induced by the nicotinic partial agonist cytisine","volume":"40","author":"Mineur","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/ajmg.b.31155","article-title":"Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy","volume":"156B","author":"Sarginson","year":"2011","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"713","DOI":"10.2217\/pgs.15.34","article-title":"Effect of the rs1051730-rs16969968 variant and smoking cessation treatment: A meta-analysis","volume":"16","author":"Leung","year":"2015","journal-title":"Pharmacogenomics"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Yano, N., and Fedulov, A.V. (2023). Targeted DNA Demethylation: Vectors, Effectors and Perspectives. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051334"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1007\/s00213-018-4921-9","article-title":"The contribution of agonist and antagonist activities of alpha4beta2* nAChR ligands to smoking cessation efficacy: A quantitative analysis of literature data","volume":"235","author":"Rollema","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1017\/S0033291718003069","article-title":"Cigarette smoking and personality: Interrogating causality using Mendelian randomisation","volume":"49","author":"Sallis","year":"2019","journal-title":"Psychol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.annepidem.2023.04.019","article-title":"A predictive algorithm to identify ever smoking in medical claims-based epidemiologic studies","volume":"85","author":"Faust","year":"2023","journal-title":"Ann. Epidemiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.1038\/s41467-020-19265-z","article-title":"Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits","volume":"11","author":"Quach","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lee, S.H., Ahn, W.Y., Seweryn, M., and Sadee, W. (2018). Combined genetic influence of the nicotinic receptor gene cluster CHRNA5\/A3\/B4 on nicotine dependence. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5219-3"},{"key":"ref_83","first-page":"1","article-title":"Helping smokers quit through pharmacogenetics","volume":"11","author":"Lerman","year":"2006","journal-title":"LDI Issue Brief."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S2213-2600(15)00283-0","article-title":"Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): A genetic association study in UK Biobank","volume":"3","author":"Wain","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Clayton, E.W., Halverson, C.M., Sathe, N.A., and Malin, B.A. (2018). A systematic literature review of individuals\u2019 perspectives on privacy and genetic information in the United States. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204417"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1064\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:36:23Z","timestamp":1788496583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":85,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091064"],"URL":"https:\/\/doi.org\/10.3390\/genes17091064","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}