New insights into the genetics of addiction

Abstract

Drug addiction is a common brain disorder that is extremely costly to the individual and to society. Genetics contributes significantly to vulnerability to this disorder, but identification of susceptibility genes has been slow. Recent genome-wide linkage and association studies have implicated several regions and genes in addiction to various substances, including alcohol and, more recently, tobacco. Current efforts aim not only to replicate these findings in independent samples but also to determine the functional mechanisms of these genes and variants.

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Figure 1: Chromosomal locations of peaks or intervals for addiction to multiple substances.

References

  1. 1

    Kreek, M. J., Nielsen, D. A., Butelman, E. R. & LaForge, K. S. Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nature Neurosci. 8, 1450–1457 (2005).

    CAS  PubMed  Google Scholar 

  2. 2

    Rutter, J. L. Symbiotic relationship of pharmacogenetics and drugs of abuse. AAPS J. 8, E174–E184 (2008).

    Google Scholar 

  3. 3

    Goldman, D., Oroszi, G. & Ducci, F. The genetics of addictions: uncovering the genes. Nature Rev. Genet. 6, 521–532 (2005).

    CAS  PubMed  Google Scholar 

  4. 4

    Li, M. D., Cheng, R., Ma, J. Z. & Swan, G. E. A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins. Addiction 98, 23–31 (2003).

    PubMed  Google Scholar 

  5. 5

    Uhl, G. R., Liu, Q. R. & Naiman, D. Substance abuse vulnerability loci: converging genome scanning data. Trends Genet. 18, 420–425 (2002).

    CAS  PubMed  Google Scholar 

  6. 6

    Lee, A. M. et al. CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Biol. Psychiatry 62, 635–641 (2007).

    CAS  PubMed  Google Scholar 

  7. 7

    Li, M. D. Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses. Hum. Genet. 123, 119–131 (2008).

    CAS  PubMed  Google Scholar 

  8. 8

    Agrawal, A. & Lynskey, M. T. Are there genetic influences on addiction: evidence from family, adoption and twin studies. Addiction 103, 1069–1081 (2008).

    PubMed  PubMed Central  Google Scholar 

  9. 9

    Madden, P. A. et al. The genetics of smoking persistence in men and women: a multicultural study. Behav. Genet. 29, 423–431 (1999).

    CAS  PubMed  Google Scholar 

  10. 10

    Tsuang, M. T. et al. Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs. Am. J. Med. Genet. 67, 473–477 (1996).

    CAS  PubMed  Google Scholar 

  11. 11

    Kendler, K. S. & Prescott, C. A. Cocaine use, abuse and dependence in a population-based sample of female twins. Br. J. Psychiatry 173, 345–350 (1998).

    CAS  PubMed  Google Scholar 

  12. 12

    True, W. R. et al. Common genetic vulnerability for nicotine and alcohol dependence in men. Arch. Gen. Psychiatry 56, 655–661 (1999).

    CAS  PubMed  Google Scholar 

  13. 13

    Long, J. C. 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. 81, 216–221 (1998).

    CAS  PubMed  Google Scholar 

  14. 14

    Reich, T. et al. Genome-wide search for genes affecting the risk for alcohol dependence. Am. J. Med. Genet. 81, 207–215 (1998).

    CAS  PubMed  Google Scholar 

  15. 15

    Saccone, N. L. et al. A genome screen of maximum number of drinks as an alcoholism phenotype. Am. J. Med. Genet. 96, 632–637 (2000).

    CAS  PubMed  Google Scholar 

  16. 16

    Osier, M. V. et al. A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Am. J. Hum. Genet. 71, 84–99 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Shea, S. H., Wall, T. L., Carr, L. G. & Li, T. K. ADH2 and alcohol-related phenotypes in Ashkenazic Jewish American college students. Behav. Genet. 31, 231–239 (2001).

    CAS  PubMed  Google Scholar 

  18. 18

    Higuchi, S., Muramatsu, T., Matsushita, S., Murayama, M. & Hayashida, M. Polymorphisms of ethanol-oxidizing enzymes in alcoholics with inactive ALDH2. Hum. Genet. 97, 431–434 (1996).

    CAS  PubMed  Google Scholar 

  19. 19

    Osier, M. et al. Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. Am. J. Hum. Genet. 64, 1147–1157 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Edenberg, H. J. et al. Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis. Hum. Mol. Genet. 15, 1539–1549 (2006).

    CAS  PubMed  Google Scholar 

  21. 21

    Osier, M. V. et al. Possible epistatic role of ADH7 in the protection against alcoholism. Am. J. Med. Genet. B Neuropsychiatr Genet. 126B, 19–22 (2004).

    CAS  PubMed  Google Scholar 

  22. 22

    Zinn-Justin, A. & Abel, L. Genome search for alcohol dependence using the weighted pairwise correlation linkage method: interesting findings on chromosome 4. Genet. Epidemiol. 17 (Suppl. 1), S421–S426 (1999).

    PubMed  Google Scholar 

  23. 23

    Porjesz, B. et al. Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes. Biol. Psychol. 61, 229–248 (2002).

    PubMed  Google Scholar 

  24. 24

    Edenberg, H. J. et al. Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am. J. Hum. Genet. 74, 705–714 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Covault, J., Gelernter, J., Hesselbrock, V., Nellissery, M. & Kranzler, H. R. Allelic and haplotypic association of GABRA2 with alcohol dependence. Am. J. Med. Genet. B Neuropsychiatr. Genet. 129, 104–109 (2004).

    Google Scholar 

  26. 26

    Lappalainen, J. et al. Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population. Alcohol Clin. Exp. Res. 29, 493–498 (2005).

    CAS  Google Scholar 

  27. 27

    Fehr, C. et al. Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Psychiatr. Genet. 16, 9–17 (2006).

    PubMed  Google Scholar 

  28. 28

    Beuten, J. et al. Single- and multilocus allelic variants within the GABAB receptor subunit 2 (GABAB2) gene are significantly associated with nicotine dependence. Am. J. Hum. Genet. 76, 859–864 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Bergen, A. W., Korczak, J. F., Weissbecker, K. A. & Goldstein, A. M. A genome-wide search for loci contributing to smoking and alcoholism. Genet. Epidemiol. 17 (Suppl. 1), S55–S60 (1999).

    PubMed  Google Scholar 

  30. 30

    Li, M. D. et al. A genome-wide scan to identify loci for smoking rate in the Framingham Heart Study population. BMC Genet. 4 (Suppl. 1), S103 (2003).

    PubMed  PubMed Central  Google Scholar 

  31. 31

    Bierut, L. J. et al. A genomic scan for habitual smoking in families of alcoholics: common and specific genetic factors in substance dependence. Am. J. Med. Genet. 124A, 19–27 (2004).

    PubMed  Google Scholar 

  32. 32

    Gelernter, J. et al. Results of a genomewide linkage scan: support for chromosomes 9 and 11 loci increasing risk for cigarette smoking. Am. J. Med. Genet. 128B, 94–101 (2004).

    PubMed  Google Scholar 

  33. 33

    Li, M. D. The genetics of nicotine dependence. Curr. Psychiatry Rep. 8, 158–164 (2006).

    CAS  PubMed  Google Scholar 

  34. 34

    Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).

    CAS  PubMed  Google Scholar 

  35. 35

    Feng, Y. 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. 75, 112–121 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Li, M. D. et al. Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence. Hum. Mol. Genet. 14, 1211–1219 (2005).

    CAS  PubMed  Google Scholar 

  37. 37

    Hutchison, K. E. et al. CHRNA4 and tobacco dependence: from gene regulation to treatment outcome. Arch. Gen. Psychiatry 64, 1078–1086 (2007).

    CAS  PubMed  Google Scholar 

  38. 38

    Conti, D. V. et al. Nicotinic acetylcholine receptor β2 subunit gene implicated in a systems-based candidate gene study of smoking cessation. Hum. Mol. Genet. 17, 2834–2848 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Lou, X. Y. et al. A generalized combinatorial approach for detecting gene-by-gene and gene-by-environment interactions with application to nicotine dependence. Am. J. Hum. Genet. 80, 1125–1137 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Li, M. D., Lou, X. Y., Chen, G., Ma, J. Z. & Elston, R. C. Gene–gene interactions among CHRNA4, CHRNB2, BDNF, and NTRK2 in nicotine dependence. Biol. Psychiatry 64, 951–957 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Marubio, L. M. et al. Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature 398, 805–810 (1999).

    CAS  PubMed  Google Scholar 

  42. 42

    Picciotto, M. R. et al. Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature 374, 65–67 (1995).

    CAS  Google Scholar 

  43. 43

    Ehringer, M. A. et al. Association of the neuronal nicotinic receptor β2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B, 596–604 (2007).

    CAS  PubMed  Google Scholar 

  44. 44

    Hatsukami, D. K., Stead, L. F. & Gupta, P. C. Tobacco addiction. Lancet 371, 2027–2038 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Steensland, P., Simms, J. A., Holgate, J., Richards, J. K. & Bartlett, S. E. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc. Natl Acad. Sci. USA 104, 12518–12523 (2007).

    CAS  PubMed  Google Scholar 

  46. 46

    Amos, C. I. et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nature Genet. 40, 616–622 (2008).

    CAS  PubMed  Google Scholar 

  47. 47

    Hung, R. J. et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452, 633–637 (2008).

    CAS  PubMed  Google Scholar 

  48. 48

    Thorgeirsson, T. E. et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452, 638–642 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Saccone, S. F. et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3,713 SNPs. Hum. Mol. Genet. 16, 36–49 (2007).

    CAS  PubMed  Google Scholar 

  50. 50

    Berrettini, W. et al. α-5/α-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol. Psychiatry 13, 368–373 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Weiss, R. B. et al. A candidate gene approach identifies the CHRNA5A3B4 region as a risk factor for age-dependent nicotine addiction. PLoS Genet. 4, e1000125 (2008).

    PubMed  PubMed Central  Google Scholar 

  52. 52

    Wang, J. C. et al. Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence. Mol. Psychiatry 15 Apr 2008 (doi:10.1038/mp.2008.42).

    PubMed  PubMed Central  Google Scholar 

  53. 53

    Grucza, R. A. et al. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence. Biol. Psychiatry 64, 922–929 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Burmeister, M., McInnis, M. G. & Zollner, S. Psychiatric genetics: progress amid controversy. Nature Rev. Genet. 9, 527–540 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Bierut, L. J. et al. Variants in nicotinic receptors and risk for nicotine dependence. Am. J. Psychiatry 165, 1163–1171 (2008).

    PubMed  PubMed Central  Google Scholar 

  56. 56

    Agrawal, A. et al. Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case–control study. Addiction 103, 1027–1038 (2008).

    PubMed  Google Scholar 

  57. 57

    Drgon, T., D'Addario, C. & Uhl, G. R. Linkage disequilibrium, haplotype and association studies of a chromosome 4 GABA receptor gene cluster: candidate gene variants for addictions. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 854–860 (2006).

    CAS  PubMed  Google Scholar 

  58. 58

    Agrawal, A. et al. An autosomal linkage scan for cannabis use disorders in the nicotine addiction genetics project. Arch. Gen. Psychiatry 65, 713–721 (2008).

    PubMed  Google Scholar 

  59. 59

    Neville, M. J., Johnstone, E. C. & Walton, R. T. Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum. Mutat. 23, 540–545 (2004).

    CAS  PubMed  Google Scholar 

  60. 60

    Gelernter, J. et al. Haplotype spanning TTC12 and ANKK1, flanked by the DRD2 and NCAM1 loci, is strongly associated to nicotine dependence in two distinct American populations. Hum. Mol. Genet. 15, 3498–3507 (2006).

    CAS  PubMed  Google Scholar 

  61. 61

    Huang, W. et al. Significant association of ANKK1 and detection of a functional polymorphism with nicotine dependence in an African-American sample. Neuropsychopharmacology 34, 319–330 (2009).

    CAS  PubMed  Google Scholar 

  62. 62

    Dick, D. M. et al. Family-based association analyses of alcohol dependence phenotypes across DRD2 and neighboring gene ANKK1. Alcohol Clin. Exp. Res. 31, 1645–1653 (2007).

    CAS  PubMed  Google Scholar 

  63. 63

    Yang, B. Z. et al. Association of haplotypic variants in DRD2, ANKK1, TTC12 and NCAM1 to alcohol dependence in independent case control and family samples. Hum. Mol. Genet. 16, 2844–2853 (2007).

    CAS  PubMed  Google Scholar 

  64. 64

    Yang, B. Z. et al. Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence. Alcohol Clin. Exp. Res. 32, 2117–2127 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Uhl, G. R. et al. Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify 'connectivity constellation' and drug target genes with pleiotropic effects. Ann. N. Y. Acad. Sci. 1141, 318–381 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Nussbaum, J. et al. Significant association of the neurexin-1 gene (NRXN1) with nicotine dependence in European- and African-American smokers. Hum. Mol. Genet. 17, 1569–1577 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Bierut, L. J. et al. Novel genes identified in a high-density genome wide association study for nicotine dependence. Hum. Mol. Genet. 16, 24–35 (2007).

    CAS  PubMed  Google Scholar 

  68. 68

    Hishimoto, A. et al. Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms. Hum. Mol. Genet. 16, 2880–2891 (2007).

    CAS  PubMed  Google Scholar 

  69. 69

    Lachman, H. M. et al. Genomewide suggestive linkage of opioid dependence to chromosome 14q. Hum. Mol. Genet. 16, 1327–1334 (2007).

    CAS  PubMed  Google Scholar 

  70. 70

    Kim, H. G. et al. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82, 199–207 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Rujescu, D. et al. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum. Mol. Genet. 22 Oct 2008 (doi:10.1093/hmg/ddn351).

    PubMed  PubMed Central  Google Scholar 

  72. 72

    Picciotto, M. R. et al. Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. Nature 391, 173–177 (1998).

    CAS  PubMed  Google Scholar 

  73. 73

    Marubio, L. M. et al. Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors. Eur. J. Neurosci. 17, 1329–1337 (2003).

    CAS  PubMed  Google Scholar 

  74. 74

    Salas, R. et al. The nicotinic acetylcholine receptor subunit α5 mediates short-term effects of nicotine in vivo. Mol. Pharmacol. 63, 1059–1066 (2003).

    CAS  PubMed  Google Scholar 

  75. 75

    Salas, R., Pieri, F. & De Biasi, M. Decreased signs of nicotine withdrawal in mice null for the β4 nicotinic acetylcholine receptor subunit. J. Neurosci. 24, 10035–10039 (2004).

    CAS  PubMed  Google Scholar 

  76. 76

    Salas, R., Cook, K. D., Bassetto, L. & De Biasi, M. The α3 and β4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology 47, 401–407 (2004).

    CAS  PubMed  Google Scholar 

  77. 77

    Tapper, A. R. et al. Nicotine activation of α4* receptors: sufficient for reward, tolerance, and sensitization. Science 306, 1029–1032 (2004).

    CAS  PubMed  Google Scholar 

  78. 78

    Labarca, C. et al. Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety. Proc. Natl Acad. Sci. USA 98, 2786–2791 (2001).

    CAS  PubMed  Google Scholar 

  79. 79

    Crabbe, J. C. Review. Neurogenetic studies of alcohol addiction. Philos. Trans. R. Soc. Lond. B 363, 3201–3211 (2008).

    Google Scholar 

  80. 80

    Buck, K. J. & Hood, H. M. Genetic association of a GABAA receptor γ2 subunit variant with severity of acute physiological dependence on alcohol. Mamm. Genome 9, 975–978 (1998).

    CAS  PubMed  Google Scholar 

  81. 81

    Blednov, Y. A. et al. Deletion of the α1 or β2 subunit of GABAA receptors reduces actions of alcohol and other drugs. J. Pharmacol. Exp. Ther. 304, 30–36 (2003).

    CAS  PubMed  Google Scholar 

  82. 82

    Hu, J. H. et al. Up-regulation of γ-aminobutyric acid transporter I mediates ethanol sensitivity in mice. Neuroscience 123, 807–812 (2004).

    CAS  PubMed  Google Scholar 

  83. 83

    Buck, K. J. & Finn, D. A. Genetic factors in addiction: QTL mapping and candidate gene studies implicate GABAergic genes in alcohol and barbiturate withdrawal in mice. Addiction 96, 139–149 (2001).

    CAS  PubMed  Google Scholar 

  84. 84

    Ponomarev, I. et al. Transcriptional signatures of cellular plasticity in mice lacking the α1 subunit of GABAA receptors. J. Neurosci. 26, 5673–5683 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Scott, L. J. et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341–1345 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, Washington DC, 1994).

  87. 87

    World Health Organization. International classification of disease (ICD-10) World Health Organization[online] (2009).

  88. 88

    Fagerstrom, K. O. Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict. Behav. 3, 235–241 (1978).

    CAS  PubMed  Google Scholar 

  89. 89

    Heatherton, T. F., Kozlowski, L. T., Frecker, R. C. & Fagerström, K. O. The Fagerström test for nicotine dependence: a revision of the Fagerström tolerance questionnaire. Br. J. Addict. 86, 1119–1127 (1991).

    CAS  PubMed  Google Scholar 

  90. 90

    Shadel, W. G., Shiffman, S., Niaura, R., Nichter, M. & Abrams, D. B. Current models of nicotine dependence: what is known and what is needed to advance understanding of tobacco etiology among youth. Drug Alcohol. Depend. 59 (Suppl. 1), S9–S22 (2000).

    PubMed  Google Scholar 

  91. 91

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

    PubMed  Google Scholar 

  92. 92

    Shiffman, S., Waters, A. & Hickcox, M. The nicotine dependence syndrome scale: a multidimensional measure of nicotine dependence. Nicotine Tob. Res. 6, 327–348 (2004).

    CAS  PubMed  Google Scholar 

  93. 93

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

    PubMed  Google Scholar 

  94. 94

    Munafo, M. R., Clark, T. G., Johnstone, E. C., Murphy, F. G. & Walton, R. T. The genetics basis for smoking behavior: a systematic review and meta-analysis. Nicotine Tob. Res. 6, 583–597 (2004).

    CAS  PubMed  Google Scholar 

  95. 95

    Stapleton, J. A., Sutherland, G. & O'Gara, C. Association between dopamine transporter genotypes and smoking cessation: a meta-analysis. Addict. Biol. 12, 221–226 (2007).

    CAS  PubMed  Google Scholar 

  96. 96

    Munafo, M. R., Matheson, I. J. & Flint, J. Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case–control studies and evidence of publication bias. Mol. Psychiatry 12, 454–461 (2007).

    CAS  PubMed  Google Scholar 

  97. 97

    Smith, L., Watson, M., Gates, S., Ball, D. & Foxcroft, D. Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: a HuGE gene–disease association review. Am. J. Epidemiol. 167, 125–138 (2008).

    PubMed  Google Scholar 

  98. 98

    Foll, B. L., Gallo, A., Le Strat, Y., Lu, L. & Gorwood, P. Genetics of dopamine receptors and drug addiction: a comprehensive review. Behav. Pharmacol. 20, 1–17 (2009).

    PubMed  Google Scholar 

  99. 99

    Li, M. D., Ma, J. Z. & Beuten, J. Progress in searching for susceptibility loci and genes for smoking-related behaviour. Clin. Genet. 66, 382–392 (2004).

    CAS  PubMed  Google Scholar 

  100. 100

    Marcos, M., Pastor, I., Gonzalez-Sarmiento, R. & Laso, F. J. Interleukin-10 gene polymorphism is associated with alcoholism but not with alcoholic liver disease. Alcohol Alcohol. 43, 523–528 (2008).

    CAS  PubMed  Google Scholar 

  101. 101

    Gratacos, M. et al. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case–control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol. Psychiatry 61, 911–922 (2007).

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are supported by grants from the National Institutes of Health (DA12844, DA-13,783, DA15462S1, AA012217, and AA016104). The authors thank C. Seneviratne, J. Wang and J. Z. Ma of the University of Virginia for assistance in the preparation of tables and figures.

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Correspondence to Ming D. Li.

Supplementary information

Supplementary Information S1 (Table 1)

Candidate genes associated with at least one drug addiction (PDF 320 kb)

Supplementary Information S2 (Table 2)

Candidate genes having one or more variants that have been associated with one substance (PDF 298 kb)

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Glossary

Behavioural automaticity

Control of behaviour by external stimuli and events in the immediate environment, often without knowledge or awareness of such control.

Behavioural saliency

In the context of this article, the likelihood and the degree to which a stimulus elicits a reaction or response.

Depression induction

A procedure that induces a state of depression.

Endophenotype

In psychiatry, a biomarker for a behavioural symptom that has a clear genetic connection.

Genetic heterogeneity

Causation of a disorder or trait by different genetic variants in different samples. This can arise when participants of different ethnic origins are included, genetic effects or samples are small, and marker density is low.

Haplotype

A combination of the alleles at different loci on the same chromosome.

Heritability

The proportion of phenotypic variance that can be attributed to variance of the genotype.

Linkage mapping

Linkage refers to the tendency of two close loci on the same chromosome to co-segregate within a pedigree. Genome-wide linkage scanning can identify loci that are involved in conditions for which there is no a priori reason to suspect any contribution.

Long-term potentiation

The long-lasting improvement in communication between two neurons that results from stimulating them simultaneously.

Multifactor dimensionality reduction method

A data reduction approach for detecting combinations of attributes or independent variables that interact to influence a binary outcome.

Positional candidate gene approach

A candidate gene-based association study that focuses on a genome region identified from linkage analysis.

QTL mapping

The statistical study of the genetic loci that contribute to variations in a quantitative trait or phenotype.

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Li, M., Burmeister, M. New insights into the genetics of addiction. Nat Rev Genet 10, 225–231 (2009). https://doi.org/10.1038/nrg2536

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