Skip to main content

Advertisement

Log in

The genetics of nicotine dependence

  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Despite almost two decades of intensive tobacco-control efforts, approximately 23% of American adults continue to smoke, and 13% are nicotine-dependent. Cigarette smoking is the greatest preventable cause of cancer, accounting for at least 30% of all cancer deaths and 87% of lung cancer deaths. Smoking behavior is in.uenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that the heritability of liability for nicotine dependence (ND) is at least 50%. During the past several years, signi.cant efforts have been made to identify susceptibility genes for ND using both genome-wide linkage and association analysis approaches. It is expected that identi.cation of susceptibility genes for ND will allow the development and tailoring of both prevention strategies for individuals at risk and effective treatment programs and medicines for individuals who use tobacco products. This review summarizes the recent progress in genetic studies of ND. As genotyping technology is being improved and well-characterized clinical samples on smoking behavior become available, more and more genes and genetic variants responsible for ND will be identi.ed in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Centers for Disease Control and Prevention: Cigarette smoking among adults — United States, 2002. Morb Mortal Wkly Rep 2004, 53:427–431.

    Google Scholar 

  2. Mokdad AH, Marks JS, Stroup DF, Gerberding JL: Actual causes of death in the United States, 2000. JAMA 2004, 291:1238–1245.

    Article  PubMed  Google Scholar 

  3. Peto R, Darby S, Deo H, et al.: Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. Br Med J 2000, 321:323–329.

    Article  CAS  Google Scholar 

  4. Vineis P, Alavanja M, Buffler P, et al.: Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 2004, 96:99–106.

    Article  PubMed  CAS  Google Scholar 

  5. Li MD: The genetics of smoking related behavior: a brief review. Am J Med Sci 2003, 326:168–173.

    Article  PubMed  Google Scholar 

  6. Sullivan PF, Kendler KS: The genetic epidemiology of smoking. Nicotine Tob Res 1999, 1:S51-S57.

    PubMed  Google Scholar 

  7. Li MD, Cheng R, Ma JZ, et al.: A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins. Addiction 2003, 98:23–31. This study presents a meta-analysis of 17 reported twin studies on the estimates of heritability and shared and unique environmental effects for smoking initiation and smoking dependence in male and female smokers.

    Article  PubMed  Google Scholar 

  8. Bergen AW, Korczak JF, Weissbecker KA, et al.: A genomewide search for loci contributing to smoking and alcoholism. Genet Epidemiol 1999, 17:S55-S60.

    PubMed  Google Scholar 

  9. Duggirala R, Almasy L, Blangero J: Smoking behavior is under the influence of a major quantitative trait locus on human chromosome 5q. Genet Epidemiol 1999, 17:S139-S144.

    PubMed  Google Scholar 

  10. Li MD, Ma JZ, Cheng R, et al.: A genome wide scan to identify loci for smoking quantity in the Framingham Heart Study populations. BMC Gene 2003, 4 (Suppl I):S103. This article presents the most signi.cant results providing evidence for linkage of smoking dependence to various human chromosomes.

    Article  Google Scholar 

  11. Straub RE, Sullivan PF, Ma Y, et al.: Susceptibility genes for nicotine dependence: a genome scan and followup in an independent sample suggest that regions on chromosomes 2, 4, 10, 16, 17 and 18 merit further study. Mol Psychiatry 1999, 4:129–144. This was the first published genome-wide linkage study that was designed speci.cally to target nicotine dependence.

    Article  PubMed  CAS  Google Scholar 

  12. Bierut LJ, Rice JP, Goate A, et al.: A genomic scan for habitual smoking in families of alcoholics: common and speci.c genetic factors in substance dependence. Am J Med Genet 2004, 124A:19–27.

    Article  PubMed  Google Scholar 

  13. Gelernter J, Liu X, Hesselbrock V, et al.: Results of a genomewide linkage scan: support for chromosomes 9 and 11 loci increasing risk for cigarette smoking. Am J Med Genet 2004, 128B:94–01.

    Article  PubMed  Google Scholar 

  14. Wang D, Ma JZ, Li MD: Mapping and veri.cation of susceptibility loci for smoking quantity using permutation linkage analysis. Pharmacogenomics J 2005, 5:166–172.

    Article  PubMed  CAS  Google Scholar 

  15. Li MD, Ma JZ, Beuten J: Progress in searching for susceptibility loci and genes for smoking-related behavior. Clin Genet 2004, 66:382–392.

    Article  PubMed  CAS  Google Scholar 

  16. Munafo MR, Clark TG, Johnstone EC, et al.: The genetic basis for smoking behavior: a systematic review and meta-analysis. Nicotine Tob Res 2004, 6:583–597. This study presents an updated review of candidate gene-based association studies for nicotine dependence.

    Article  PubMed  CAS  Google Scholar 

  17. Jonsson EG, Nothen MM, Grunhage F, et al.: Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry 1999, 4:290–296.

    Article  PubMed  CAS  Google Scholar 

  18. Thompson J, Thomas N, Singleton A, et al.: D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 1997, 7:479–484.

    Article  PubMed  CAS  Google Scholar 

  19. Tyndale RF: Genetics of alcohol and tobacco use in humans. Ann Med 2003, 35:94–121.

    Article  PubMed  CAS  Google Scholar 

  20. Kaupmann K, Malitschek B, Schuler V, et al.: GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 1998, 396:683–687.

    Article  PubMed  CAS  Google Scholar 

  21. Corrigall WA, Coen KM, Adamson KL, et al.: Response of nicotine self-administration in the rat to manipulations of mu-opioid and gamma-aminobutyric acid receptors in the ventral tegmental area. Psychopharmacology (Berl) 2000, 149:107–114.

    Article  CAS  Google Scholar 

  22. Fattore L, Cossu G, Martellotta MC, et al.: Baclofen antagonizes intravenous self-administration of nicotine in mice and rats. Alcohol Alcohol 2002, 37:495–498.

    PubMed  CAS  Google Scholar 

  23. Beuten J, Ma JZ, Payne TJ, et al.: Single- and multilocus allelic variants within the GABAB receptor subunit 2 (GABAB2) gene are signi.cantly associated with nicotine dependence. Am J Hum Genet 2005, 76:859–864. This article represents the first positional candidate gene that was selected on the basis of genome-wide linkage analysis results and found to be signi.cantly associated with nicotine dependence.

    Article  PubMed  CAS  Google Scholar 

  24. Heatherton TF, Kozlowski LT, Frecker RC, et al.: The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 1991, 86:1119–1127.

    Article  PubMed  CAS  Google Scholar 

  25. Heatherton TF, Kozlowski LT, Frecker RC, et al.: Measuring the heaviness of smoking: using self-reported time to the first cigarette of the day and number of cigarettes smoked per day. Br J Addict 1989, 84:791–799.

    Article  PubMed  CAS  Google Scholar 

  26. Flores CM, Rogers SW, Pabreza LA, et al.: A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. Mol Pharmacol 1992, 41:31–37.

    PubMed  CAS  Google Scholar 

  27. Marks MJ, Pauly JR, Gross SD, et al.: Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. J Neurosci 1992, 12:2765–2784.

    PubMed  CAS  Google Scholar 

  28. Whiteaker P, Sharples CG, Wonnacott S: Agonist-induced up-regulation of alpha4beta2 nicotinic acetylcholine receptors in M10 cells: pharmacological and spatial definition. Mol Pharmacol 1998, 53:950–962.

    PubMed  CAS  Google Scholar 

  29. Li MD, Beuten J, Ma JZ, et al.: Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence. Hum Mol Genet 2005, 14:1211–1219.

    Article  PubMed  CAS  Google Scholar 

  30. Feng Y, Niu T, Xing H, et al.: A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men. Am J Hum Genet 2004, 75:112–121.

    Article  PubMed  CAS  Google Scholar 

  31. Lueders KK, Hu S, McHugh L, et al.: Genetic and functional analysis of single nucleotide polymorphisms in the beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2). Nicotine Tob Res 2002, 4:115–125.

    Article  PubMed  CAS  Google Scholar 

  32. Silverman MA, Neale MC, Sullivan PF, et al.: Haplotypes of four novel single nucleotide polymorphisms in the nicotinic acetylcholine receptor beta2-subunit (CHRNB2) gene show no association with smoking initiation or nicotine dependence. Am J Med Genet 2000, 96:646–653.

    Article  PubMed  CAS  Google Scholar 

  33. Ma JZ, Beuten J, Payne TJ, et al.: Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence. Hum Mol Genet 2005, 14:1691–1698.

    Article  PubMed  CAS  Google Scholar 

  34. Matsushita S, Kimura M, Miyakawa T, et al.: Association study of brain-derived neurotrophic factor gene polymorphism and alcoholism. Alcohol Clin Exp Res 2004, 28:1609–1612.

    Article  PubMed  CAS  Google Scholar 

  35. Itoh K, Hashimoto K, Shimizu E, et al.: Association study between brain-derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan. Am J Med Genet B Neuropsychiatr Genet 2005, 132:70–73.

    PubMed  Google Scholar 

  36. Liu QR, Walther D, Drgon T, et al.: Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson’s Disease. Am J Med Genet B Neuropsychiatr Genet 2005, 134:93–103.

    PubMed  Google Scholar 

  37. Beuten J, Ma JZ, Payne TJ, et al.: Significant association of BDNF haplotypes in European-American male smokers but not in European-American female or African-American smokers. Am J Med Genet B Neuropsychiatr Genet 2005, 139:73–80.

    PubMed  Google Scholar 

  38. Weinshilboum RM, Otterness DM, Szumlanski CL: Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu Rev Pharmacol Toxicol 1999, 39:19–52.

    Article  PubMed  CAS  Google Scholar 

  39. Akil M, Kolachana BS, Rothmond DA, et al.: Catechol-Omethyltransferase genotype and dopamine regulation in the human brain. J Neurosci 2003, 23:2008–2013.

    PubMed  CAS  Google Scholar 

  40. Gogos JA, Morgan M, Luine V, et al.: Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc Natl Acad Sci U S A 1998, 95:9991–9996.

    Article  PubMed  CAS  Google Scholar 

  41. David SP, Johnstone E, Griffiths SE, et al.: No association between functional catechol O-methyl transferase 1947A>G polymorphism and smoking initiation, persistent smoking or smoking cessation. Pharmacogenetics 2002, 12:265–268.

    Article  PubMed  CAS  Google Scholar 

  42. McKinney EF, Walton RT, Yudkin P, et al.: Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers. Pharmacogenetics 2000, 10:483–491.

    Article  PubMed  CAS  Google Scholar 

  43. Beuten J, Payne TJ, Ma JZ, et al.: Significant association of catechol-O-methyltransferase (COMT) haplotypes with nicotine dependence in male and female smokers of two ethnic populations. Neuropsychopharmacology. 2005 [Epub ahead of print].

  44. Swan GE, Hudmon KS, Jack LM, et al.: Environmental and genetic determinants of tobacco use: methodology for a multidisciplinary, longitudinal family-based investigation. Cancer Epidemiol Biomarkers Prev 2003, 12:994–1005.

    PubMed  Google Scholar 

  45. Colby SM, Tiffany ST, Shiffman S, et al.: Measuring nicotine dependence among youth: a review of available approaches and instruments. Drug Alcohol Depend 2000, 59:S23-S39.

    Article  PubMed  Google Scholar 

  46. Gilliard J, Bruchon-Schweitzer M: Development and validation of a multidimensional smoking behaviour questionnaire. Psychol Rep 2001, 89:499–509.

    Article  PubMed  CAS  Google Scholar 

  47. Moolchan ET, Radzius A, Epstein DH, et al.: The Fagerstrom Test for Nicotine Dependence and the Diagnostic Interview Schedule: do they diagnose the same smokers? Addict Behav 2002, 27:101–113.

    Article  PubMed  Google Scholar 

  48. Shiffman S, Kassel JD, Paty J, et al.: Smoking typology pro.les of chippers and regular smokers. J Subst Abuse 1994, 6:21–35.

    Article  PubMed  CAS  Google Scholar 

  49. Russell MA, Peto J, Patel UA: The classi.cation of smoking by factorial structure of motives. J Royal Statist Soc Assoc 1974, 137:313–334.

    Google Scholar 

  50. Hudmon KS, Marks JL, Pomerleau CS, et al.: A multidimensional model for characterizing tobacco dependence. Nicotine Tob Res 2003, 5:655–664.

    Article  PubMed  Google Scholar 

  51. Fagerstrom KO: Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict Behav 1978, 3:235–241.

    Article  PubMed  CAS  Google Scholar 

  52. Tiffany ST: A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. Psychol Rev 1990, 97:147–168.

    Article  PubMed  CAS  Google Scholar 

  53. Shadel WG, Shiffman S, Niaura R, et al.: Current models of nicotine dependence: what is known and what is needed to advance understanding of tobacco etiology among youth. Drug Alcohol Depend 2000, 59:S9-S22.

    Article  PubMed  Google Scholar 

  54. Robinson TE, Berridge KC: The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 1993, 18:247–291.

    Article  PubMed  CAS  Google Scholar 

  55. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Association; 1994.

    Google Scholar 

  56. Johnson EO, Breslau N, Anthony JC: The latent dimensionality of DIS/DSM-III-R nicotine dependence: exploratory analyses. Addiction 1996, 91:583–588.

    Article  PubMed  CAS  Google Scholar 

  57. Piper ME, Piasecki TM, Federman EB, et al.: A multiple motives approach to tobacco dependence: the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68). J Consult Clin Psychol 2004, 72:139–154.

    Article  PubMed  Google Scholar 

  58. Shiffman S, Hickcox M, Gnys M, et al.: The nicotine dependence syndrome scale: development of a new measure. Annual meeting of the Society for Research on Nicotine and Tobacco: San Diego, CA, 1995.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ming D. Li PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, M.D. The genetics of nicotine dependence. Curr Psychiatry Rep 8, 158–164 (2006). https://doi.org/10.1007/s11920-006-0016-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-006-0016-0

Keywords

Navigation