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The genetics of alcohol dependence

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Abstract

Alcohol dependence is a common, complex disorder, which affects millions of people worldwide and causes considerable burden in terms of interpersonal and societal costs. Family, twin, and adoption studies have convincingly demonstrated that genes play an important role in the development of alcohol dependence, with heritability estimates in the range of 50% to 60% for both men and women. A number of studies are under way to identify specific genes involved in the predisposition toward alcohol dependence, and there is reason to be enthusiastic about recent progress. Several associated susceptibility genes are reviewed here, including genes involved in alcohol metabolism, as well as genes involved in GABAergic, endogenous opioid, dopaminergic, cholinergic, and serotonergic transmission. The next challenge will be to further characterize the risk associated with these susceptibility genes, examining how they may be related to comorbid disorders, developmental trajectories of risk, and potential moderation by environmental factors.

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References and Recommended Reading

  1. Kessler RC, McGonagle KA, Zhao S, et al.: Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994, 51:8–19.

    PubMed  CAS  Google Scholar 

  2. Harwood H: Updating estimates of the economic costs of alcohol abuse in the United States: estimates, update methods, and data. Report prepared by The Lewin Group for the National Institute on Alcohol Abuse and Alcoholism, 2000. Based on The Economic Costs of Alcohol and Drug Abuse in the United States 1992. Report Prepared for the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services. NIH Publication No. 98-4327. Edited by Harwood H, Fountain D, and Livermore G. Rockville, MD: National Institutes of Health; 1998.

    Google Scholar 

  3. McGue M: The behavioral genetics of alcoholism. Curr Directions Psychol Sci 1999, 8:109–115. This paper provides an overview of family, twin, and adoption studies providing evidence for the heritability of alcohol dependence.

    Article  Google Scholar 

  4. Long JC, Knowler WC, Hanson RL, et al.: Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population. Am J Med Genet 1998, 81:216–221.

    Article  PubMed  CAS  Google Scholar 

  5. Prescott C, Sullivan PF, Myers J, et al.: The Irish Affected Sib Pair Study of Alcohol Dependence: study methodology and validation of diagnosis by interview and family history. Alcohol Clin Exp Res 2005, 29:417–429.

    Article  PubMed  Google Scholar 

  6. Ehlers CL, Gilder DA, Wall TL, et al.: Genomic screen for loci associated with alcohol dependence in Mission Indians. Am J Med Genet B Neuropsychiatr Genet 2004, 129:110–115.

    Article  PubMed  Google Scholar 

  7. Hill SY, Shen S, Zezza N, et al.: A genome wide search for alcoholism susceptibility genes. Am J Med Genet B Neuropsychiatr Genet 2004, 128:102–113.

    Article  PubMed  Google Scholar 

  8. Heath AC, Jardine R, Martin NG: Interactive effects of genotype and social environment on alcohol consumption in female twins. J Stud Alcohol 1989, 50:38–48.

    PubMed  CAS  Google Scholar 

  9. Koopmans JR, Slutske WS, van Baal GC, Boomsma DI: The in.uence of religion on alcohol use initiation: evidence for genotype X environment interaction. Behav Genet 1999, 29:445–453.

    Article  PubMed  CAS  Google Scholar 

  10. Dick DM, Rose RJ, Viken RJ, et al.: Exploring gene-environment interactions: socioregional moderation of alcohol use. J Abnorm Psychol 2001, 110:625–632.

    Article  PubMed  CAS  Google Scholar 

  11. Cloninger CR, Bohman M, Sigvardsson S: Inheritance of alcohol abuse: cross-fostering analysis of adopted men. Arch Gen Psychiatry 1981, 38:861–868.

    PubMed  CAS  Google Scholar 

  12. Gottesman II, Gould TD: The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003, 160:1–10. This paper provides an overview of the rationale and use of endophenotypes as they apply to psychiatric disorders.

    Article  Google Scholar 

  13. Porjesz B, Rangaswamy M, Kamarajan C, et al.: The utility of neurophysiological markers in the study of alcoholism. Clin Neurophysiol 2005, 116:993–1018. This paper provides an overview of the utility of neurophysiological phenotypes as they apply to alcohol dependence.

    Article  PubMed  Google Scholar 

  14. Dick DM, Foroud T: Genetic strategies to detect genes involved in alcoholism and alcohol-related traits. Alcohol Res Health 2002, 26:172–180. This paper provides an introduction to the methods used to find genes involved in complex phenotypes, such as psychiatric disorders.

    PubMed  Google Scholar 

  15. Shen YC, Fan JH, Edenberg HJ, et al.: Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism. Alcohol Clin Exp Res 1997, 21:1272–1277.

    PubMed  CAS  Google Scholar 

  16. Neumark YD, Friedlander Y, Thomasson HR, Li T-K: Association of the ADH2*2 allele with reduced ethanol consumption in Jewish men in Israel: a pilot study. J Stud Alcohol 1998, 59:133–139.

    PubMed  CAS  Google Scholar 

  17. Whitfield JB, Nightingale BN, Bucholz KK, et al.: ADH genotypes and alcohol use and dependence in Europeans. Alcohol Clin Exp Res 1998, 22:1463–1469.

    PubMed  CAS  Google Scholar 

  18. Saccone N, Kwon JM, Corbett J, et al.: A genome screen of maximum number of drinks as an alcoholism phenotype. Neuropsychiat Genet 2000, 96:632–637.

    Article  CAS  Google Scholar 

  19. Birley AJ, Whit.eld JB, Neale MC, et al.: Genetic timeseries analysis identi.es a major QTL for in vivo alcohol metabolism not predicted by in vitro studies of structural protein polymorphism at the ADH1B or ADH1C loci. Behav Genet 2005, 35:509–524.

    Article  PubMed  CAS  Google Scholar 

  20. Lou X, Kranzler HR, Zuo L, et al.: ADH4 gene variation is associated with alcohol dependence and drug dependence in European Americans: results from HWD tests and case-control association studies. Neuropsychopharmacology 2005, 1:1–11.

    Google Scholar 

  21. Prescott C, Sullivan PF, Kuo PH, et al.: Linkage of alcohol dependence symptoms to chromosome 4 and preliminary association with ADH-7 in the Irish Affected Sib Pair Study of Alcohol Dependence. Alcohol Clin Exp Res 2005, 29(Suppl 5):132A.

    Google Scholar 

  22. Uhl GR, Liu Q-R, Walther D, et al.: Polysubstance abuse-vulnerability genes: genome scans for association, using 1004 subjects and 1494 single-nucleotide polymorphisms. Am J Hum Genet 2001, 69:1290–1300.

    Article  PubMed  CAS  Google Scholar 

  23. Harada S, Agarwal DP, Goedde HW, et al.: Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan [letter]. Lancet 1982, 2(8302):827.

    Article  PubMed  CAS  Google Scholar 

  24. Chen WJ, Loh E-W, Hsu Y-P, et al.: Alcohol-metabolising genes and alcoholism among Taiwanese Han men: independent effect of ADH2, ADH3, and ALDH2. Br J Psychiatry 1996, 168:762–767.

    Article  PubMed  CAS  Google Scholar 

  25. Grobin AC, Matthews DB, Devaud LL, Morrow AL: The role of GABA-A receptors in the acute and chronic effects of ethanol. Psychopharmacology 1998, 139:2–19.

    Article  PubMed  CAS  Google Scholar 

  26. Williams JT, Begleiter H, Porjesz B, et al.: Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. II. Alcoholism and event-related potentials. Am J Hum Genet 1999, 65:1148–1160.

    Article  PubMed  CAS  Google Scholar 

  27. Porjesz B, Almasy L, Edenberg HJ, et al.: Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus. Proc Natl Acad Sci U S A 2002, 99:3729–3733.

    Article  PubMed  CAS  Google Scholar 

  28. Edenberg HJ, Dick DM, Xuei X, et al.: Variations in GABRA2, encoding the a2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet 2004, 74:705–714.

    Article  PubMed  CAS  Google Scholar 

  29. Covault J, Gelernter J, Hesselbrock V, et al.: Allelic and haplotypic association of GABRA2 with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 2004, 129:104–109.

    Article  PubMed  Google Scholar 

  30. Lappalainen J, Krupitsky E, Remizov M, et al.: Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population. Alcohol Clin Exp Res 2005, 29:493–498.

    Article  PubMed  CAS  Google Scholar 

  31. Noble EP, Zhang X, Ritchie T, et al.: D2 dopamine receptor and GABA(A) receptor beta3 subunit genes and alcoholism. Psychiatry Res 1998, 81:133–147.

    Article  PubMed  CAS  Google Scholar 

  32. Dick DM, Edenberg HJ, Xuei X, et al.: Association of GABRG3 with alcohol dependence. Alcohol Clin Exp Res 2004, 28:4–9.

    Article  PubMed  CAS  Google Scholar 

  33. Buck KJ: Molecular genetic analysis of the role of GABAergic systems in the behavioral and cellular actions of alcohol. Behav Genet 1996, 26:313–323.

    Article  PubMed  CAS  Google Scholar 

  34. Ray LA, Hutchison KE: A polymorphism of the mu-opioid receptor gene (OPRM1) and sensitivity to the effects of alcohol in humans. Alcohol Clin Exp Res 2004, 28:1789–1795.

    Article  PubMed  CAS  Google Scholar 

  35. Bart G, Kreek MJ, Ott J, et al.: Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden. Neuropsychopharmacology 2005, 2:417–422.

    Article  CAS  Google Scholar 

  36. Bergen AW, Kokoszka J, Peterson R, et al.: Mu opioid receptor gene variants: lack of association with alcohol dependence. Mol Psychiatry 1997, 2:490–494.

    Article  PubMed  CAS  Google Scholar 

  37. Wang JC, Hinrichs AL, Stock H, et al.: Evidence of common and speci.c genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet 2004, 13:1903–1911.

    Article  PubMed  CAS  Google Scholar 

  38. Luo X, Kranzler HR, Zuo L, et al.: CHRM2 gene predisposes to alcohol dependence, drug dependence, and affective disorders: results from an extended case-control structured association study. Hum Mol Genet 2005, 14:2421–2432.

    Article  PubMed  CAS  Google Scholar 

  39. Jones KA, Porjesz B, Almasy L, et al.: Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: Implications for human brain dynamics and cognition. Int J Psychophysiol 2004, 53:75–90.

    Article  PubMed  Google Scholar 

  40. Blum K, Noble EP, Sheridan PJ, et al.: Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 1990, 263:2055–2060.

    Article  PubMed  CAS  Google Scholar 

  41. Parsian A, Todd RD, Devor EJ, et al.: Alcoholism and alleles of the human D2 dopamine receptor locus. Arch Gen Psychiatry 1991, 48:655–663.

    PubMed  CAS  Google Scholar 

  42. Gelernter J, O’Malley S, Risch N, et al.: No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism. JAMA 1991, 266:1801–1807.

    Article  PubMed  CAS  Google Scholar 

  43. Feinn R, Nellissery M, Kranzler HR: Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 2005, 133B:79–84.

    Article  PubMed  Google Scholar 

  44. Munafo MR, Lingford-Hughes AR, Johnstone EC, Walton RT: Association between the serotonin transporter gene and alcohol consumption in social drinkers. Am J Med Genet B Neuropsychiatr Genet 2005, 135B:10–14.

    Article  PubMed  Google Scholar 

  45. Hinrichs AL, Wang JC, Bufe B, et al.: Functional variant in a bitter-taste receptor (hTAS2R16) influences risk for alcohol dependence. Am J Hum Genet 2006, 78:103–111.

    Article  PubMed  CAS  Google Scholar 

  46. Duffy VB, Davidson AC, Kidd JR, et al.: Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake. Alcohol Clin Exp Res 2004, 28:1629–1637.

    Article  PubMed  CAS  Google Scholar 

  47. Agrawal A, Edenberg HJ, Foroud T, et al.: Association of GABRA2 with drug dependence in the Collaborative Study of the Genetics of Alcoholism sample. Behav Genet 2006, In press.

  48. Dick DM, Agrawal A, Schuckit M, et al.: Marital status, alcohol dependence, and GABRA2: evidence for geneenvironment correlation and interaction. J Stud Alcohol 2005, In press.

  49. Dick DM, Bierut L, Hinrichs AL, et al.: The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages. Behav Genet. 2005, In press.

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Authors and Affiliations

  1. Department of Psychiatry, 660 South Euclid Avenue, Box 8134, 63130, St. Louis, MO, USA

    Laura J. Bierut MD

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  1. Danielle M. Dick PhD
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  2. Laura J. Bierut MD
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Correspondence to Laura J. Bierut MD.

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Dick, D.M., Bierut, L.J. The genetics of alcohol dependence. Curr Psychiatry Rep 8, 151–157 (2006). https://doi.org/10.1007/s11920-006-0015-1

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