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Genetics of Alcoholism

  • Genetic Disorders (W Berrettini, Section Editor)
  • Published:
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Abstract

Alcohol use and alcohol use disorders are substantially heritable. Variants in genes coding for alcohol metabolic enzymes have long been known to influence consumption. More recent studies in family-based samples have implicated GABRA2, nicotinic receptor genes such as CHRNB3, and a number of other specific single genes as associated with alcohol use disorders. The growing use of genetic analyses, in particular studies using polygenic risk scores; neurobiologic pathways; and methods for quantifying gene × gene and gene × environment interactions have also contributed to an evolving understanding of the genetic architecture of alcohol use disorders. Additionally, the study of behavioral traits associated with alcohol dependence such as impulsivity and sensation seeking, and the influences of demographic factors (i.e., sex and ethnicity) have significantly enhanced the genetics of alcoholism literature. This article provides a brief overview of the current topically relevant findings in the field to date and includes areas of research still requiring attention.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. CDC. http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm (2013). Posted on Dec 26, 2013.

  2. Moss HB. Impact of alcohol on society: a brief overview. Soc Work Public Health. 2013;28:175–7.

    Article  PubMed  Google Scholar 

  3. Diagnostic and Statistical Manual of Mental Disorders. 1994.

  4. American Psychiatric Association. 2013. DSM 5. American Psychiatric Association.

  5. Kendler KS, Heath AC, Neale MC, Kessler RC, Eaves LJ. A population-based twin study of alcoholism in women. Jama. 1992;268(14):1877–82.

    Article  CAS  PubMed  Google Scholar 

  6. Kendler KS, Karkowski-Shuman L. Stressful life events and genetic liability to major depression: genetic control of exposure to the environment? Psychol Med. 1997;27(03):539–47.

    Article  CAS  PubMed  Google Scholar 

  7. Heath AC, Bucholz KK, Madden PAF, Dinwiddie SH, Slutske WS, Bierut LJ, et al. Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med. 1997;27(6):1381–96.

    Article  CAS  PubMed  Google Scholar 

  8. Kendler KS, Gardner CO. Boundaries of major depression: an evaluation of DSM-IV criteria. Am J Psychiatr. 1998;155(2):172–7.

    CAS  PubMed  Google Scholar 

  9. Bohman M, Sigvardsson S, Cloninger CR. Maternal inheritance of alcohol abuse: cross-fostering analysis of adopted women. Arch Gen Psychiatry. 1981;38(9):965–9.

    Article  CAS  PubMed  Google Scholar 

  10. Cloninger CR, Bohman M, Sigvardsson S. Inheritance of alcohol abuse: cross-fostering analysis of adopted men. Arch Gen Psychiatry. 1981;38(8):861.

    Article  CAS  PubMed  Google Scholar 

  11. Goodwin DW, Schulsinger F, Knop J, Mednick S, Guze SB. Alcoholism and depression in adopted-out daughters of alcoholics. Arch Gen Psychiatry. 1977;34(7):751.

    Article  CAS  PubMed  Google Scholar 

  12. Zheng Y, Heagerty PJ, Hsu L, Newcomb PA. On combining family‐based and population‐based case–control data in association studies. Biometrics. 2010;66(4):1024–33.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Nurnberger JI, Wiegand R, Bucholz K, O’Connor S, Meyer ET, Reich T, et al. A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependentprobands. Arch Gen Psychiatry. 2004;61(12):1246–56.

    Article  PubMed  Google Scholar 

  14. Reich T, Edenberg HJ, Goate A, et al. Genome-wide search for genes affecting the risk for alcohol dependence. Am J Med Genet. 1998;81(3):207–15.

    Article  CAS  PubMed  Google Scholar 

  15. Long JC, Knowler WC, Hanson RL, Robin RW, Urbanek M, Moore E, 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(3):216–21.

    Article  CAS  PubMed  Google Scholar 

  16. Gizer IR, Ehlers CL, Vieten C, Seaton-Smith KL, Feiler HS, Lee JV, et al. Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study. Drug Alcohol Depend. 2011;113(2):125–32.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Edenberg H. Alcoholism. In: Nurnberger Jr JI, Berrettini W, editors. Principles of psychiatric genetics. Cambridge: Cambridge University Press; 2012.

    Google Scholar 

  18. Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996;273(5281):1516–7.

    Article  CAS  PubMed  Google Scholar 

  19. Kwon JM, Goate AM. The candidate gene approach. Alcohol Res Health. 2000;24(3):164–8.

    CAS  PubMed  Google Scholar 

  20. Strachan T, Read AP. Molecular pathology. 1999.

  21. Ehlers CL. Variations in ADH and ALDH in Southwest California Indians. Alcohol Res Health. 2007;30(1):14–7. Review.

    PubMed Central  PubMed  Google Scholar 

  22. Shen YC, Fan JH, Edenberg HJ, Li TK, Cui YH, Wang YF, 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(7):1272–7.

    Article  CAS  PubMed  Google Scholar 

  23. Edenberg HJ, Foroud T. Review: The genetics of alcoholism: identifying specific genes through family studies. Addict Biol. 2006;11(3–4):386–96.

    Article  PubMed  Google Scholar 

  24. Park BL, Kim JW, Cheong HS, Kim LH, Lee BC, Seo CH, et al. Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication. Hum Genet. 2013;132(6):657–68.

    Article  CAS  PubMed  Google Scholar 

  25. Edenberg HJ, Dick DM, Xuei X, Tian H, Almasy L, Bauer LO, et al. Variations in<i>GABRA2,</i>encoding the α2 subunit of the GABA<sub>A</sub>receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet. 2004;74(4):705–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Covault J, Gelernter J, Hesselbrock V, Nellissery M, Kranzler HR. Allelic and haplotypic association of GABRA2 with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2004;129(1):104–9.

    Article  Google Scholar 

  27. Enoch MA. Genetic and environmental influences on the development of alcoholism. Ann N Y Acad Sci. 2006;1094(1):193–201.

    Article  PubMed  Google Scholar 

  28. Fehr C, Sander T, Tadic A, Lenzen KP, Anghelescu I, Klawe C, et al. Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Psychiatr Genet. 2006;16(1):9–17.

    Article  PubMed  Google Scholar 

  29. Soyka M, Preuss UW, Hesselbrock V, Zill P, Koller G, Bondy B. GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence. J Psychiatr Res. 2008;42(3):184–91.

    Article  CAS  PubMed  Google Scholar 

  30. Dick D M, Cho S B, Latendresse S J, Aliev F, Nurnberger J I, Edenberg H J, et al. Genetic influences on alcohol use across stages of development: GABRA2 and longitudinal trajectories of drunkenness from adolescence to young adulthood. Addict Biol. 2013.

  31. Dick DM, Bierut L, Hinrichs A, Fox L, Bucholz KK, Kramer J, et al. The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages. Behav Genet. 2006;36(4):577–90.

    Article  PubMed  Google Scholar 

  32. Dick DM, Aliev F, Latendresse S, Porjesz B, Schuckit M, Rangaswamy M, et al. How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity. Twin Res Hum Genet. 2013;16(03):661–9. Study suggests that later risk for alcohol problems may actually begin with an initial predisposition to sensation seeking.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Trucco E M, Villafuerte S, Heitzeg M M, Burmeister M, Zucker R A. Rule breaking mediates the developmental association between GABRA2 and adolescent substance abuse. J Child Psychol Psychiatry. 2014. This study found that the effect of GABRA2 on problematic drinking appears to be mediated by increased rule breaking in mid-adolescence.

  34. Wang JC, Hinrichs AL, Stock H, Budde J, Allen R, Bertelsen S, et al. Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet. 2004;13(17):1903–11.

    Article  CAS  PubMed  Google Scholar 

  35. Jones KA, Porjesz B, Almasy L, Bierut L, Dick D, Goate A, et al. A cholinergic receptor gene (CHRM2) affects event-related oscillations. Behav Genet. 2006;36(5):627–39.

    Article  PubMed  Google Scholar 

  36. Dick DM, Agrawal A. The genetics of alcohol and other drug dependence. Alcohol Res Health. 2008;31(2):111.

    PubMed Central  PubMed  Google Scholar 

  37. Noble EP. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Genet B Neuropsychiatr Genet. 2003;116(1):103–25.

    Article  Google Scholar 

  38. Dick DM, Wang JC, Plunkett J, Aliev F, Hinrichs A, Bertelsen S, et al. Family-based association analyses of alcohol dependence phenotypes across DRD2 and neighboring gene ANKK1. Alcohol Clin Exp Res. 2007;1645–53.

  39. Mota NR, Bau CH, Banaschewski T, Buitelaar JK, Ebstein RP, Franke B, et al. Association between DRD2/DRD4 interaction and conduct disorder: a potential developmental pathway to alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2013;162(6):546–9.

    Article  CAS  Google Scholar 

  40. Hammoumi S, Payen A, Favre JD, Balmes JL, Benard JY, Husson M, et al. Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence? Alcohol. 1999;17(2):107–12.

    Article  CAS  PubMed  Google Scholar 

  41. Dick DM, Plunkett J, Hamlin D, Nurnberger Jr J, Kuperman S, Schuckit M, et al. Association analyses of the serotonin transporter gene with lifetime depression and alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample. Psychiatr Genet. 2007;17(1):35–8.

    Article  PubMed  Google Scholar 

  42. Porjesz B, Almasy L, Edenberg HJ, Wang K, Chorlian DB, Foroud T, et al. Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus. Proc Natl Acad Sci. 2002;99(6):3729–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Rangaswamy M, Porjesz B. Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes. Brain Res. 2008;1235:153–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Agrawal A, Grant JD, Waldron M, Duncan AE, Scherrer JF, Lynskey MT, et al. Risk for initiation of substance use as a function of age of onset of cigarette, alcohol and cannabis use: findings in a Midwestern female twin cohort. Prev Med. 2006;43(2):125–8.

  45. Agrawal A, Wetherill L, Bucholz KK, Kramer J, Kuperman S, Lynskey MT, et al. Genetic influences on craving for alcohol. Addict Behav. 2013;38(2):1501–8. An initial study finding genetic links to craving.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Dick DM, Edenberg HJ, Xuei X, Goate A, Kuperman S, Schuckit M, et al. Association of GABRG3 with alcohol dependence. Alcohol Clin Exp Res. 2004;28(1):4–9.

    Article  CAS  PubMed  Google Scholar 

  47. Li D, Sulovari A, Cheng C, Zhao H, Kranzler HR, Gelernter J. Association of gamma-aminobutyric acid A receptor α2 gene(GABRA2) with alcohol use disorder. Neuropsychopharmacology. 2013;39(4):907–18.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Loh EW, Smith I, Murray R, McLaughlin M, McNulty S, Ball D. Association between variants at the GABAAbeta2, GABAAalpha6 and GABAAgamma2 gene cluster and alcohol dependence in a Scottish population. Mol Psychiatry. 1999;4(6):539–44.

    Article  CAS  PubMed  Google Scholar 

  49. Loh EW, Ball D. Role of the GABA (A) beta2, GABA (A) alpha6, GABA (A) alpha1 and GABA (A) gamma2 receptor subunit genes cluster in drug responses and the development of alcohol dependence. Neurochem Int. 1999;37(5–6):413–23.

    Google Scholar 

  50. Sander T, Ball D, Murray R, Patel J, Samochowiec J, Winterer G, et al. Association analysis of sequence variants of the GABAAα6, β2, and γ2 gene cluster and alcohol dependence. Alcohol Clin Exp Res. 1999;23(3):427–31.

    Article  CAS  PubMed  Google Scholar 

  51. Noble EP, Zhang X, Ritchie T, Lawford BR, Grosser SC, Young RM, et al. D<sub>2</sub>dopamine receptor and GABA<sub>A</sub>receptor β3 subunit genes and alcoholism. Psychiatry Res. 1998;81(2):133–47.

    Article  CAS  PubMed  Google Scholar 

  52. Dick DM, Agrawal A, Schuckit MA, Bierut L, Hinrichs A, Fox L, et al. Marital status, alcohol dependence, and GABRA2: evidence for gene-environment correlation and interaction. J Stud Alcohol Drugs. 2006;67(2):185.

    Article  Google Scholar 

  53. Jones KA, Porjesz B, Almasy L, Bierut L, Goate A, Wang JC, et al. Linkage and linkage disequilibrium of evoked EEG oscillations with<i>CHRM2</i>receptor gene polymorphisms: implications for human brain dynamics and cognition. Int J Psychophysiol. 2004;53(2):75–90.

    Article  PubMed  Google Scholar 

  54. Porjesz B, Rangaswamy M. Neurophysiological endophenotypes, CNS disinhibition, and risk for alcohol dependence and related disorders. Sci World J. 2007;7:131–41.

    Article  Google Scholar 

  55. Wang JC, Hinrichs AL, Bertelsen S, Stock H, Budde JP, Dick DM, et al. Functional variants in TAS2R38 and TAS2R16 influence alcohol consumption in high-risk families of African-American origin. Alcohol Clin Exp Res. 2007;31(2):209–15.

    Article  PubMed  CAS  Google Scholar 

  56. Hinrichs AL, Wang JC, Bufe B, Kwon JM, Budde J, Allen R, et al. Functional variant in a bitter-taste receptor (<i>hTAS2R16</i>) influences risk of alcohol dependence. Am J Hum Genet. 2006;78(1):103–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Wang JC, Cruchaga C, Saccone NL, Bertelsen S, Liu P, Budde JP, et al. Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Genet. 2009;18(16):3125–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Grucza RA, Wang JC, Stitzel JA, Hinrichs AL, Saccone SF, Saccone NL, et al. A risk allele for nicotine dependence in<i>CHRNA5</i>is a protective allele for cocaine dependence. Biol Psychiatry. 2008;64(11):922–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Saccone NL, Wang JC, Breslau N, Johnson EO, Hatsukami D, Saccone SF, et al. The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. Cancer Res. 2009;69(17):6848–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Xuei X, Dick D, Flury-Wetherill L, Tian HJ, Agrawal A, Bierut L, et al. Association of the κ-opioid system with alcohol dependence. Mol Psychiatry. 2006;11(11):1016–24.

    Article  CAS  PubMed  Google Scholar 

  61. Xuei X, Flury-Wetherill L, Bierut L, Dick D, Nurnberger J, Foroud T, et al. The opioid system in alcohol and drug dependence: family-based association study. Am J Med Genet B Neuropsychiatr Genet. 2007;144(7):877–84.

    Article  CAS  Google Scholar 

  62. Wang KS, Liu X, Zhang Q, Pan Y, Aragam N, Zeng M. A meta-analysis of two genome-wide association studies identifies 3 new loci for alcohol dependence. J Psychiatr Res. 2011;45(11):1419–25.

    Article  PubMed  Google Scholar 

  63. Enoch MA. Genetic influences on the development of alcoholism. Curr Psychiatry Rep. 2013;15(11):1–9.

    Article  Google Scholar 

  64. Zuo L, Zhang F, Zhang H, Zhang XY, Wang F, Li CSR, et al. Genome-wide search for replicable risk gene regions in alcohol and nicotine co-dependence. Am J Med Genet B Neuropsychiatr Genet. 2012;159(4):437–44.

    Article  CAS  Google Scholar 

  65. Gelernter J, Kranzler H R, Sherva R, Almasy L, Koesterer R, Smith A H, et al. Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci. Mol Psychiatry. 2013.

  66. Olfson E, Bierut LJ. Convergence of genome-wide association and candidate gene studies for alcoholism. Alcohol Clin Exp Res. 2012;36(12):2086–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Frank J, Cichon S, Treutlein J, Ridinger M, Mattheisen M, Hoffmann P, et al. Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster. Addict Biol. 2012;17(1):171–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Guo X, Liu Z, Wang X, Zhang H. Large scale association analysis for drug addiction: results from SNP to gene. Sci World J. 2012.

  69. Meyers JL, Dick DM. Genetic and environmental risk factors for adolescent-onset substance use disorders. Child Adolesc Psychiatr Clin N Am. 2010;19(3):465–77.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Chen AC, Manz N, Tang Y, Rangaswamy M, Almasy L, Kuperman S, et al. Single-nucleotide polymorphisms in cortico-tropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. Alcohol Clin Exp Res. 2010;34(6):988–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Hodgkinson CA, Yuan Q, Xu K., Shen PH, Heinz E, Lobos EA, Goldman D. Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol 2008;43(5):505–515.

  72. Sher KJ, Dick DM, Crabbe JC, Hutchison KE, O’Malley SS, Heath AC. Review: Consilient research approaches in studying gene×environment interactions in alcohol research. Addict Biol. 2010;15(2):200–16.

    Article  PubMed Central  PubMed  Google Scholar 

  73. Foroud T, Wetherill LF, Kramer J, Tischfield JA, Nurnberger JI, Schuckit MA, et al. The tachykinin receptor 3 is associated with alcohol and cocaine dependence. Alcohol Clin Exp Res. 2008;32(6):1023–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Edenberg HJ, Xuei X, Wetherill LF, Bierut L, Bucholz K, Dick DM, et al. Association of NFKB1, which encodes a subunit of the transcription factor NF-κB, with alcohol dependence. Hum Mol Genet. 2008;17(7):963–70.

    Article  CAS  PubMed  Google Scholar 

  75. Kendler KS, Kalsi G, Holmans PA, Sanders AR, Aggen SH, Dick DM, et al. Genomewide association analysis of symptoms of alcohol dependence in the molecular genetics of schizophrenia (MGS2) control sample. Alcohol Clin Exp Res. 2011;35(5):963–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Samochowiec J, Kucharska-Mazur J, Grzywacz A, Jabłoński M, Rommelspacher H, Samochowiec A, et al. Family-based and case-control study of DRD2, DAT, 5HTT, COMT genes polymorphisms in alcohol dependence. Neurosci Lett. 2006;410(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  77. Derringer J, Krueger RF, Dick DM, Saccone S, Grucza RA, Agrawal A, et al. Predicting sensation seeking from dopamine genes a candidate-system approach. Psychol Sci. 2010;21(9):1282–90.

    Article  PubMed Central  PubMed  Google Scholar 

  78. Edenberg HJ, Foroud T, Koller DL, Goate A, Rice J, Eerdewegh P, et al. A family-based analysis of the association of the dopamine D2 receptor (DRD2) with alcoholism. Alcohol Clin Exp Res. 1998;22(2):505–12.

    Article  CAS  PubMed  Google Scholar 

  79. Derringer J, Krueger RF, Dick DM, Aliev F, Grucza RA, Saccone S, et al. The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach. Behav Genet. 2012;42(4):626–35.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Dick DM, Foroud T. Candidate genes for alcohol dependence: a review of genetic evidence from human studies. Alcohol Clin Exp Res. 2003;27(5):868–79.

    Article  PubMed  Google Scholar 

  81. Belsky J, Pluess M, Widaman KF. Confirmatory and competitive evaluation of alternative gene-environment interaction hypotheses. J Child Psychol Psychiatry. 2013;54(10):1135–43.

    Article  PubMed  Google Scholar 

  82. Agrawal A, Hinrichs AL, Dunn G, Bertelsen S, Dick DM, Saccone SF, et al. Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample. Drug Alcohol Depend. 2008;93(1):12–20.

    Article  PubMed Central  PubMed  Google Scholar 

  83. Chen AC, Tang Y, Rangaswamy M, Wang JC, Almasy L, Foroud T, et al. Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2009;150(3):359–68.

    Article  CAS  Google Scholar 

  84. Karpyak VM, Geske JR, Colby CL, Mrazek DA, Biernacka JM. Genetic variability in the NMDA-dependent AMPA trafficking cascade is associated with alcohol dependence. Addict Biol. 2012;17(4):798–806.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Kimura M, Higuchi S. Genetics of alcohol dependence. Psychiatry Clin Neurosci. 2011;65(3):213–25.

    Article  CAS  PubMed  Google Scholar 

  86. Zuo L, Zhang XY, Wang F, Li CSR, Lu L, Ye L, et al. Genome-wide significant association signals in IPO11-HTR1A region specific for alcohol and nicotine codependence. Alcohol Clin Exp Res. 2013;37(5):730–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Morozova TV, Goldman D, Mackay TF, Anholt RR. The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks. Genome Biol. 2012;13(2):239.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Foroud T, Wetherill LF, Liang T, Dick DM, Hesselbrock V, Kramer J, et al. Association of alcohol craving with α-synuclein (SNCA). Alcohol Clin Exp Res. 2007;31(4):537–45.

    CAS  PubMed  Google Scholar 

  89. Vandenbergh DJ, Rodriguez LA, Hivert E, Schiller JH, Villareal G, Pugh EW, et al. Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: no interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene. Am J Med Genet. 2000;96(5):678–83.

    Article  CAS  PubMed  Google Scholar 

  90. Zuo L, Zhang CK, Wang F, Li CSR, Zhao H, Lu L, et al. A novel, functional and replicable risk gene region for alcohol dependence identified by genome-wide association study. PLoS One. 2011;6(11):e26726.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Hesselbrock V M, Foroud T, Edenberg H, Nurnberger J I Jr, Reich T, Rice J P. Genetics and alcoholism: the COGA Project. Alcohol Health Dis. 2001;103–24.

  92. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Treutlein J, Cichon S, Ridinger M, et al. Genome-wide association study of alcohol dependence. Arch Gen Psychiatry. 2009;66(7):773–84. doi:10.1001/archgenpsychiatry.2009.83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Kapoor M, Wang JC, Wetherill L, Le N, Bertelsen S, Hinrichs AL, et al. A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks. Hum Genet. 2013;132(10):1141–51.

    Article  PubMed Central  PubMed  Google Scholar 

  95. Heath AC, Whitfield JB, Martin NG, Pergadia ML, Goate AM, Lind PA, et al. A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications. Biol Psychiatry. 2011;70(6):513–8.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, et al. A genome-wide association study of alcohol dependence. Proc Natl Acad Sci. 2010;107(11):5082–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Edenberg HJ, Koller DL, Xuei X, Wetherill L, McClintick JN, Almasy L, et al. Genome-wide association study of alcohol dependence implicates a region on chromosome 11. Alcohol Clin Exp Res. 2010;34(5):840–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Zlojutro M, Manz N, Rangaswamy M, Xuei X, Flury-Wetherill L, Koller D, et al. Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2011;156(1):44–58.

    Article  CAS  Google Scholar 

  99. Wang JC, Foroud T, Hinrichs AL, Le NX, Bertelsen S, Budde JP, et al. A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Mol Psychiatry. 2012;18(11):1218–24.

    Article  PubMed  CAS  Google Scholar 

  100. Edwards AC, Aliev F, Bierut LJ, Bucholz KK, Edenberg H, Hesselbrock V, et al. Genome-wide association study of comorbid depressive syndrome and alcohol dependence. Psychiatr Genet. 2012;22(1):31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Yu W, Yesupriya A, Wulf A, Hindorff LA, Dowling N, Khoury MJ, et al. GWAS Integrator: a bioinformatics tool to explore human genetic associations reported in published genome-wide association studies. Eur J Hum Genet. 2011;19(10):1095–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Lin P, Hartz SM, Wang JC, Agrawal A, Zhang TX, McKenna N, et al. Copy number variations in 6q14. 1 and 5q13. 2 are associated with alcohol dependence. Alcohol Clin Exp Res. 2012;36(9):1512–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  103. Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, Redon R, et al. Diet and the evolution of human amylase gene copy number variation. Nat Genet. 2007;39(10):1256–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Malhotra D, Sebat J. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell. 2012;148(6):1223–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Haller G, Kapoor M, Budde J, Xuei X, Edenberg H, Nurnberger J, et al. Rare missense variants in CHRNB3 and CHRNA3 are associated with risk of alcohol and cocaine dependence. Hum Mol Genet. 2014;23(3):810–9. An initial study that assessed rare variants in CHRNB3. The results indicated that among European Americans, carriers of missense variants in CHRNB3 had increased DSM-IV AD symptoms.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Farris SP, Miles MF. Ethanol modulation of gene networks: implications for alcoholism. Neurobiol Dis. 2012;45(1):115–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  107. Kos MZ, Yan J, Dick DM, Agrawal A, Bucholz KK, Rice JP, et al. Common biological networks underlie genetic risk for alcoholism in African- and European-American populations. Genes Brain Behav. 2013;12(5):532–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  108. Zhu J, Zhang B, Smith EN, Drees B, Brem RB, Kruglyak L, et al. Integrating large-scale functional genomic data to dissect the complexity of yeast regulatory networks.

  109. Yang Y et al. Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types. Nat Commun. 2014;5:3231.

    PubMed Central  PubMed  Google Scholar 

  110. Yan J, Aliev F, Webb B T, Kendler K S, Williamson V S, Edenberg H J, et al. Using genetic information from candidate gene and genome-wide association studies in risk prediction for alcohol dependence. Addict Biol. 2013.

  111. Vink J M, Hottenga J J, Geus E J, Willemnsen G, Neale M C, Furberg H, Boomsma D I. Polygenic risk scores for smoking: predictors for alcohol and cannabis use? Addiction. 2014.

  112. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatr. 2003;160(4):636–45.

    Article  PubMed  Google Scholar 

  113. Begleiter H, Porjesz B. Genetics of human brain oscillations. Int J Psychophysiol. 2006;60(2):162–71.

    Article  PubMed  Google Scholar 

  114. Lejuez CW, Magidson JF, Mitchell SH, Sinha R, Stevens MC, De Wit H. Behavioral and biological indicators of impulsivity in the development of alcohol use, problems, and disorders. Alcohol Clin Exp Res. 2010;34(8):1334–45.

    PubMed Central  CAS  PubMed  Google Scholar 

  115. Soloff PH, Lynch KG, Moss HB. Serotonin, impulsivity, and alcohol use disorders in the older adolescent: a psychobiological study. Alcohol Clin Exp Res. 2000;24(11):1609–19.

    Article  CAS  PubMed  Google Scholar 

  116. Dick DM, Smith G, Olausson P, Mitchell SH, Leeman RF, O’Malley SS, et al. Review: Understanding the construct of impulsivity and its relationship to alcohol use disorders. Addict Biol. 2010;15(2):217–26.

    Article  PubMed Central  PubMed  Google Scholar 

  117. Villafuerte S, Heitzeg MM, Foley S, Yau WW, Majczenko K, Zubieta JK, et al. Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Mol Psychiatry. 2012;17(5):511–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  118. Grant JD, Vergés A, Jackson KM, Trull TJ, Sher KJ, Bucholz KK. Age and ethnic differences in the onset, persistence and recurrence of alcohol use disorder. Addiction. 2012;107(4):756–65.

    Article  PubMed Central  PubMed  Google Scholar 

  119. Nolen-Hoeksema S. Gender differences in risk factors and consequences for alcohol use and problems. Clin Psychol Rev. 2004;24(8):981–1010.

    Article  PubMed  Google Scholar 

  120. Perry BL, Pescosolido BA, Bucholz K, Edenberg H, Kramer J, Kuperman S, et al. Gender-specific gene-environment interaction in alcohol dependence: the impact of daily life events and GABRA2. Behav Genet. 2013;43(5):402–14.

    Article  PubMed  Google Scholar 

  121. Quillen E E, Chen X D, Almasy L, Yang F, He H, Li X, et al. ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample. Am J Med Genet Part B Neuropsychiatr Genet. 2013.

  122. Han S, Gelernter J, Kranzler HR, Yang BZ. Ordered subset linkage analysis based on admixture proportion identifies new linkage evidence for alcohol dependence in African-Americans. Hum Genet. 2013;132(4):397–403. By using admixture proportion as a covariate this study was able to decrease genetic heterogeneity and increase the discovery of linkage for AD in an admixed population that included AA subjects.

    Article  PubMed Central  PubMed  Google Scholar 

  123. Ittiwut C, Yang BZ, Kranzler HR, Anton RF, Hirunsatit R, Weiss RD, et al. GABRG1 and GABRA2 variation associated with alcohol dependence in African Americans. Alcohol Clin Exp Res. 2012;36(4):588–93. An initial study that found differences in African Americans in their frequency of variants of GABRAG1 and GABRA2 and their association with AD.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  124. Heilig M, Goldman D, Berrettini W, O’Brien CP. Pharmacogenetic approaches to the treatment of alcohol addiction. Nat Rev Neurosci. 2011;12(11):670–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Priya A. Iyer-Eimerbrink and John I. Nurnberger, Jr., declare that they have no conflict of interest.

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  1. Institute of Psychiatric Research, Department of Psychiatry, School of Medicine, Indiana University, 320 W. 15th Street, Indianapolis, IN, 46202, USA

    Priya A. Iyer-Eimerbrink & John I. Nurnberger Jr.

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Correspondence to Priya A. Iyer-Eimerbrink.

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Iyer-Eimerbrink, P.A., Nurnberger, J.I. Genetics of Alcoholism. Curr Psychiatry Rep 16, 518 (2014). https://doi.org/10.1007/s11920-014-0518-0

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