Current and future prospects for epigenetic biomarkers of substance use disorders

Genes

Volumn 6, Issue 4, 2015, Pages 991-1022

  Andersen, Allan M ^a   Dogan, Meeshanthini V ^a,b   Beach, Steven R H ^c,d   Philibert, Robert A ^a,b  

^a UNIVERSITY OF IOWA   (United States)

^b IA United States   (United States)

^c NONE   (United States)

^d UNIVERSITY OF GEORGIA   (United States)

Author keywords

Addiction; Alcohol; Biomarkers; Cannabis; Epigenetics; Opioids; Psychostimulants; Smoking; Substance use disorders; Tobacco

Indexed keywords

ALCOHOL; ALPHA SYNUCLEIN; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME A; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; AMPHETAMINE; AROMATIC HYDROCARBON RECEPTOR; ATRIAL NATRIURETIC FACTOR; CANNABINOID 1 RECEPTOR; CATECHOL METHYLTRANSFERASE; CODEINE; DIAMORPHINE; DNA METHYLTRANSFERASE 3B; DOPAMINE TRANSPORTER; ETHYL GLUCURONIDE; FACTOR II RECEPTOR LIKE 3; HYDROMORPHONE; LEPTIN; METHADONE; METHAMPHETAMINE; MORPHINE; MU OPIATE RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; NERVE GROWTH FACTOR; OREXIN A; OXYCODONE; PROOPIOMELANOCORTIN; PROTEINASE; SEROTONIN TRANSPORTER; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASOPRESSIN;

ALCOHOL ABUSE; CANNABIS ADDICTION; COMT GENE; CPG ISLAND; DNA METHYLATION; ELECTRONIC CIGARETTE; EPIGENETICS; GENE EXPRESSION; GENE LOCUS; HUMAN; MAO A GENE; MAO B GENE; OPIATE ADDICTION; OPRD1 GENE; OPRK1 GENE; OPRM1 GENE; RECEPTOR GENE; REVIEW; SMOKING; SYSTEMATIC REVIEW;

EID: 84945200995     PISSN: None     EISSN: 20734425     Source Type: Journal    
DOI: 10.3390/genes6040991     Document Type: Review

References (126)

1. Institute for Health Metrics and Evaluation (IHME). GBD Compare. Available online: http://vizhub.healthdata.org/gbd-compare (accessed on 17 June 2015).
2. Centers for Disease Control and Prevention (CDC).Vital signs: Current cigarette smoking among adults aged 18
3. Bouchery, E.E.; Harwood, H.J.; Sacks, J.J.; Simon, C.J.; Brewer, R.D. Economic costs of excessive alcohol consumption in the US, 2006. Am. J. Prev. Med. 2011, 41, 516–524.
4. US Department of Health and Human Services. Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings; Substance Abuse and Mental Health Services Administration: Rockville, MD, USA, 2011.
5. Staines, G.L.; Magura, S.; Foote, J.; Deluca, A.; Kosanke, N. Polysubstance use among alcoholics. J. Addict. Dis. 2001, 20, 57–73.
6. Florescu, A.; Ferrence, R.; Einarson, T.; Selby, P.; Soldin, O.; Koren, G. Methods for quantification of exposure to cigarette smoking and environmental tobacco smoke: Focus on developmental toxicology. Ther. Drug Monit. 2009, 31, 14–30.
7. Jatlow, P.; Toll, B.A.; Leary, V.; Krishnan-Sarin, S.; O’Malley, S.S. Comparison of expired carbon monoxide and plasma cotinine as markers of cigarette abstinence. Drug Alcohol. Depend. 2008, 98, 203–209.
8. Sandberg, A.; Skold, C.M.; Grunewald, J.; Eklund, A.; Wheelock, A.M. Assessing recent smoking status by measuring exhaled carbon monoxide levels. PLoS ONE 2011, 6, e28864.
9. Tavakoli, H.R.; Hull, M.; Okasinski, L.M. Review of current clinical biomarkers for the detection of alcohol dependence. Innov. Clin. Neurosci. 2011, 8, 26–33.
10. Standridge, J.B.; Adams, S.M.; Zotos, A.P. Urine drug screening: A valuable office procedure. Am. Fam. Phys. 2010, 81, 635–640.
11. Moeller, K.E.; Lee, K.C.; Kissack, J.C. Urine drug screening: Practical guide for clinicians. Mayo Clin. Proc. 2008, 83, 66–76.
12. Mikeska, T.; Craig, J.M. DNA methylation biomarkers: Cancer and beyond. Genes 2014, 5, 821–864.
13. Kissick, W.L. Medicine’s Dilemmas: Infinite Needs versus Finite Resources; Yale University Press: New Haven, CT, USA, 1994.
14. Committee, I.E.. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009, 32, 1327–1334.
15. Guintivano, J.; Brown, T.; Newcomer, A.; Jones, M.; Cox, O.; Maher, B.; Eaton, W.; Payne, J.L.; Wilcox, A.J.; Kaminsky, Z.A. Identification and replication of a combined epigenetic and genetic biomarker predicting suicide and suicidal behaviors. Am. J. Psychiatry 2014, 171, 1287–1296.
16. Jonas, D.E.; Amick, H.R.; Feltner, C.; Wines, R.; Shanahan, E.; Rowe, C.J.; Garbutt, J.C. Genetic polymorphisms and response to medications for alcohol use disorders: A systematic review and meta-analysis. Pharmacogenomics 2014, 15, 1687–1700.
17. Center for Substance Abuse Treatment. The role of biomarkers in the treatment of alcohol use disorders. Subst. Abuse Treat. Advis. 2006, 5, 1–7.
18. Ladd-Acosta, C. Epigenetic signatures as biomarkers of exposure. Curr. Environ. Health Rep. 2015, 2, 117–125.
19. Suzuki, M.M.; Bird, A. DNA methylation landscapes: Provocative insights from epigenomics. Nat. Rev. Genet. 2008, 9, 465–476.
20. Nielsen, D.A.; Utrankar, A.; Reyes, J.A.; Simons, D.D.; Kosten, T.R. Epigenetics of drug abuse: Predisposition or response. Pharmacogenomics 2012, 13, 1149–1160.
21. Vassoler, F.M.; White, S.L.; Schmidt, H.D.; Sadri-Vakili, G.; Pierce, R.C. Epigenetic inheritance of a cocaine-resistance phenotype. Nat. Neurosci. 2013, 16, 42–47.
22. Zhang, Y.; Landthaler, M.; Schlussman, S.D.; Yuferov, V.; Ho, A.; Tuschl, T.; Kreek, M.J. Mu opioid receptor knockdown in the substantia nigra/ventral tegmental area by synthetic small interfering RNA blocks the rewarding and locomotor effects of heroin. Neuroscience 2009, 158, 474–483.
23. Lasek, A.W.; Janak, P.H.; He, L.; Whistler, J.L.; Heberlein, U. Downregulation of mu opioid receptor by RNA interference in the ventral tegmental area reduces ethanol consumption in mice. Genes Brain Behav. 2007, 6, 728–735.
24. Yuferov, V.; Nielsen, D.A.; Levran, O.; Randesi, M.; Hamon, S.; Ho, A.; Morgello, S.; Kreek, M.J. Tissue-specific DNA methylation of the human prodynorphin gene in post-mortem brain tissues and PBMCs. Pharmacogenet. Genom. 2011, 21, 185–196.
25. Sun, Y.V.; Turner, S.T.; Smith, J.A.; Hammond, P.I.; Lazarus, A.; van de Rostyne, J.L.; Cunningham, J.M.; Kardia, S.L. Comparison of the DNA methylation profiles of human peripheral blood cells and transformed B-lymphocytes. Hum. Genet. 2010, 127, 651–658.
26. Houseman, E.A.; Accomando, W.P.; Koestler, D.C.; Christensen, B.C.; Marsit, C.J.; Nelson, H.H.; Wiencke, J.K.; Kelsey, K.T. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinform. 2012, doi:10.1186/1471-2105-13-86.
27. Dogan, M.V.; Shields, B.; Cutrona, C.; Gao, L.; Gibbons, F.X.; Simons, R.; Monick, M.; Brody, G.; Tan, K.; Philibert, R. The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genom. 2014, doi:10.1186/1471-2164-15-151.
28. Elliott, H.; Tillin, T.; McArdle, W.; Ho, K.; Duggirala, A.; Frayling, T.; Davey Smith, G.; Hughes, A.; Chaturvedi, N.; Relton, C. Differences in smoking associated DNA methylation patterns in South Asians and Europeans. Clin. Epigenetics 2014, 6, doi:10.1186/1868-7083-6-4.
29. Allione, A.; Marcon, F.; Fiorito, G.; Guarrera, S.; Siniscalchi, E.; Zijno, A.; Crebelli, R.; Matullo, G. Novel epigenetic changes unveiled by monozygotic twins discordant for smoking habits. PLoS ONE 2015, 10, e0128265.
30. Artis, D.; Spits, H. The biology of innate lymphoid cells. Nature 2015, 517, 293–301.
31. Zhang, F.F.; Cardarelli, R.; Carroll, J.; Fulda, K.G.; Kaur, M.; Gonzalez, K.; Vishwanatha, J.K.; Santella, R.M.; Morabia, A. Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics 2011, 6, 623–629.
32. Talhout, R.; Schulz, T.; Florek, E.; van Benthem, J.; Wester, P.; Opperhuizen, A. Hazardous compounds in tobacco smoke. Int. J. Environ. Res. Public Health 2011, 8, 613–628.
33. Slotkin, T.A. Nicotine and the adolescent brain: Insights from an animal model. Neurotoxicol. Teratol. 2002, 24, 369–384.
34. Herraiz, T.; Chaparro, C. Human monoamine oxidase is inhibited by tobacco smoke: Beta-carboline alkaloids act as potent and reversible inhibitors. Biochem. Biophys. Res. Commun. 2005, 326, 378–386.
35. Philibert, R.A.; Beach, S.R.; Gunter, T.D.; Brody, G.H.; Madan, A.; Gerrard, M. The effect of smoking on MAOA promoter methylation in DNA prepared from lymphoblasts and whole blood. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010, 153B, 619–628.
36. Philibert, R.A.; Gunter, T.D.; Beach, S.R.; Brody, G.H.; Madan, A. MAOA methylation is associated with nicotine and alcohol dependence in women. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008, 147B, 565–570.
37. Launay, J.M.; del Pino, M.; Chironi, G.; Callebert, J.; Peoc’h, K.; Megnien, J.L.; Mallet, J.; Simon, A.; Rendu, F. Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. PLoS ONE 2009, 4, e7959.
38. Xu, Q.; Ma, J.Z.; Payne, T.J.; Li, M.D. Determination of methylated CpG sites in the promoter region of catechol-O-methyltransferase (COMT) and their involvement in the etiology of tobacco smoking. Front. Psychiatry 2010, 1, doi:10.3389/fpsyt.2010.00016.
39. Toledo-Rodriguez, M.; Lotfipour, S.; Leonard, G.; Perron, M.; Richer, L.; Veillette, S.; Pausova, Z.; Paus, T. Maternal smoking during pregnancy is associated with epigenetic modifications of the brain-derived neurotrophic factor-6 exon in adolescent offspring. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010, 153B, 1350–1354.
40. Suter, M.; Abramovici, A.; Showalter, L.; Hu, M.; Shope, C.D.; Varner, M.; Aagaard-Tillery, K. In utero tobacco exposure epigenetically modifies placental CYP1A1 expression. Metabolism 2010, 59, 1481–1490.
41. Murphy, S.K.; Adigun, A.; Huang, Z.; Overcash, F.; Wang, F.; Jirtle, R.L.; Schildkraut, J.M.; Murtha, A.P.; Iversen, E.S.; Hoyo, C. Gender-specific methylation differences in relation to prenatal exposure to cigarette smoke. Gene 2012, 494, 36–43.
42. Han, W.; Wang, T.; Reilly, A.A.; Keller, S.M.; Spivack, S.D. Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients. Respir. Res. 2009, doi:10.1186/1465-9921-10-86.
43. Christensen, B.C.; Houseman, E.A.; Marsit, C.J.; Zheng, S.; Wrensch, M.R.; Wiemels, J.L.; Nelson, H.H.; Karagas, M.R.; Padbury, J.F.; Bueno, R.; et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009, 5, e1000602.
44. Breton, C.V.; Byun, H.M.; Wenten, M.; Pan, F.; Yang, A.; Gilliland, F.D. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am. J. Respir. Crit. Care Med. 2009, 180, 462–467.
45. Breitling, L.P.; Salzmann, K.; Rothenbacher, D.; Burwinkel, B.; Brenner, H. Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease. Eur. Heart J. 2012, 33, 2841–2848.
46. Breitling, L.P.; Yang, R.; Korn, B.; Burwinkel, B.; Brenner, H. Tobacco-smoking-related differential DNA methylation: 27k Discovery and replication. Am. J. Hum. Genet. 2011, 88, 450–457.
47. Wan, E.S.; Qiu, W.; Baccarelli, A.; Carey, V.J.; Bacherman, H.; Rennard, S.I.; Agusti, A.; Anderson, W.; Lomas, D.A.; Demeo, D.L. Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome. Hum. Mol. Genet. 2012, 21, 3073–3082.
48. Sun, Y.V.; Smith, A.K.; Conneely, K.N.; Chang, Q.; Li, W.; Lazarus, A.; Smith, J.A.; Almli, L.M.; Binder, E.B.; Klengel, T.; et al. Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans. Hum. Genet. 2013, 132, 1027–1037.
49. Zeilinger, S.; Kuhnel, B.; Klopp, N.; Baurecht, H.; Kleinschmidt, A.; Gieger, C.; Weidinger, S.; Lattka, E.; Adamski, J.; Peters, A.; et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS ONE 2013, 8, e63812.
50. Shenker, N.S.; Polidoro, S.; van Veldhoven, K.; Sacerdote, C.; Ricceri, F.; Birrell, M.A.; Belvisi, M.G.; Brown, R.; Vineis, P.; Flanagan, J.M. Epigenome-wide association study in the European prospective investigation into cancer and nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum. Mol. Genet. 2013, 22, 843–851.
51. Besingi, W.; Johansson, A. Smoke-related DNA methylation changes in the etiology of human disease. Hum. Mol. Genet. 2014, 23, 2290–2297.
52. Harlid, S.; Xu, Z.; Panduri, V.; Sandler, D.P.; Taylor, J.A. CpG sites associated with cigarette smoking: Analysis of epigenome-wide data from the sister study. Environ. Health Perspect. 2014, 122, 673–678.
53. Tsaprouni, L.G.; Yang, T.P.; Bell, J.; Dick, K.J.; Kanoni, S.; Nisbet, J.; Vinuela, A.; Grundberg, E.; Nelson, C.P.; Meduri, E.; et al. Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation. Epigenetics 2014, 9, 1382–1396.
54. Guida, F.; Sandanger, T.M.; Castagne, R.; Campanella, G.; Polidoro, S.; Palli, D.; Krogh, V.; Tumino, R.; Sacerdote, C.; Panico, S.; et al. Dynamics of smoking-induced genome-wide methylation changes with time since smoking cessation. Hum. Mol. Genet. 2015, 24, 2349–2359.
55. Zaghlool, S.B.; Al-Shafai, M.; Al Muftah, W.A.; Kumar, P.; Falchi, M.; Suhre, K. Association of DNA methylation with age, gender, and smoking in an Arab population. Clin. Epigenetics 2015, 7, doi:10.1186/s13148-014-0040-6.
56. Sherry, S.T.; Ward, M.-H.; Kholodov, M.; Baker, J.; Phan, L.; Smigielski, E.M.; Sirotkin, K. dbSNP: The NCBI database of genetic variation. Nucleic Acids Res. 2001, 29, 308–311.
57. Zhang, Y.; Yang, R.; Burwinkel, B.; Breitling, L.P.; Holleczek, B.; Schottker, B.; Brenner, H. F2RL3 methylation in blood DNA is a strong predictor of mortality. Int. J. Epidemiol. 2014, 43, 1215–1225.
58. Zhang, Y.; Schottker, B.; Ordonez-Mena, J.; Holleczek, B.; Yang, R.; Burwinkel, B.; Butterbach, K.; Brenner, H. F2RL3 methylation, lung cancer incidence and mortality. Int. J. Cancer 2015, 137, 1739–1748.
59. Zhang, Y.; Schottker, B.; Florath, I.; Stock, C.; Butterbach, K.; Holleczek, B.; Mons, U.; Brenner, H. Smoking-associated DNA methylation biomarkers and their predictive value for all-cause and cardiovascular mortality. Environ. Health Perspect. 2015, doi:10.1289/ehp.1409020.
60. Nguyen, L.P.; Bradfield, C.A. The search for endogenous activators of the aryl hydrocarbon receptor. Chem. Res. Toxicol. 2007, 21, 102–116.
61. Monick, M.M.; Beach, S.R.; Plume, J.; Sears, R.; Gerrard, M.; Brody, G.H.; Philibert, R.A. Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2012, 159B, 141–151.
62. Wan, E.S.; Qiu, W.; Carey, V.J.; Morrow, J.; Bacherman, H.; Foreman, M.G.; Hokanson, J.E.; Bowler, R.P.; Crapo, J.D.; DeMeo, D.L. Smoking associated site specific differential methylation in buccal mucosa in the COPDGene study. Am. J. Respir. Cell Mol. Biol. 2015, 52, 246–254.
63. Chhabra, D.; Sharma, S.; Kho, A.T.; Gaedigk, R.; Vyhlidal, C.A.; Leeder, J.S.; Morrow, J.; Carey, V.J.; Weiss, S.T.; Tantisira, K.G.; et al. Fetal lung and placental methylation is associated with in utero nicotine exposure. Epigenetics 2014, 9, 1473–1484.
64. Ivorra, C.; Fraga, M.F.; Bayon, G.F.; Fernandez, A.F.; Garcia-Vicent, C.; Chaves, F.J.; Redon, J.; Lurbe, E. DNA methylation patterns in newborns exposed to tobacco in utero. J. Transl. Med. 2015, 13, doi:10.1186/s12967-015-0384-5.
65. Philibert, R.; Beach, S.R.; Lei, M.-K.; Brody, G.H. Changes in DNA methylation at the aryl hydrocarbon receptor repressor may be a new biomarker for smoking. Clin. Epigenetics 2013, 5, doi:10.1186/1868-7083-5-19.
66. Philibert, R.A.; Beach, S.R.; Brody, G.H. Demethylation of the aryl hydrocarbon receptor repressor as a biomarker for nascent smokers. Epigenetics 2012, 7, 1331–1338.
67. Joubert, B.R.; Haberg, S.E.; Nilsen, R.M.; Wang, X.; Vollset, S.E.; Murphy, S.K.; Huang, Z.; Hoyo, C.; Midttun, O.; Cupul-Uicab, L.A.; et al. 450k Epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ. Health Perspect. 2012, 120, 1425–1431.
68. Markunas, C.A.; Xu, Z.; Harlid, S.; Wade, P.A.; Lie, R.T.; Taylor, J.A.; Wilcox, A.J. Identification of DNA methylation changes in newborns related to maternal smoking during pregnancy. Environ. Health Perspect. 2014, 122, 1147–1153.
69. Joubert, B.R.; Haberg, S.E.; Bell, D.A.; Nilsen, R.M.; Vollset, S.E.; Midttun, O.; Ueland, P.M.; Wu, M.C.; Nystad, W.; Peddada, S.D.; et al. Maternal smoking and DNA methylation in newborns: In utero effect or epigenetic inheritance? Cancer Epidemiol. Biomark. Prev. 2014, 23, 1007–1017.
70. Novakovic, B.; Ryan, J.; Pereira, N.; Boughton, B.; Craig, J.M.; Saffery, R. Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy. Epigenetics 2014, 9, 377–386.
71. Shenker, N.S.; Ueland, P.M.; Polidoro, S.; van Veldhoven, K.; Ricceri, F.; Brown, R.; Flanagan, J.M.; Vineis, P. DNA methylation as a long-term biomarker of exposure to tobacco smoke. Epidemiology 2013, 24, 712–716.
72. Philibert, R.; Hollenbeck, N.; Andersen, E.; Osborn, T.; Gerrard, M.; Gibbons, F.X.; Wang, K. A quantitative epigenetic approach for the assessment of cigarette consumption. Front. Psychol. 2015, 6, doi:10.3389/fpsyg.2015.00656.
73. Di Castelnuovo, A.; Costanzo, S.; Bagnardi, V.; Donati, M.; Iacoviello, L.; de Gaetano, G. Alcohol dosing and total mortality in men and women: An updated meta-analysis of 34 prospective studies. Arch. Intern. Med. 2006, 166, 2437–2445.
74. Poschl, G.; Seitz, H. Alcohol and cancer. Alcohol Alcohol. 2004, 39, 155–165.
75. Marron, M.; Boffetta, P.; Zhang, Z.F.; Zaridze, D.; Wunsch-Filho, V.; Winn, D.M.; Wei, Q.; Talamini, R.; Szeszenia-Dabrowska, N.; Sturgis, E.M.; et al. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int. J. Epidemiol. 2010, 39, 182–196.
76. Tuyns, A.J.; Esteve, J.; Raymond, L.; Berrino, F.; Benhamou, E.; Blanchet, F.; Boffetta, P.; Crosignani, P.; Moral, A.D.; Lehmann, W. Cancer of the larynx/hypopharynx, tobacco and alcohol: Iarc international case[1]control study in Turin and Varese (Italy), Zaragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France). Int. J. Cancer 1988, 41, 483–491.
77. Bonsch, D.; Bernd, L.; Kornhuber, J.; Bleich, S. DNA hypermethylation of the alpha synuclein promoter in patients with alcoholism. Mol. Neurosci. 2005, 16, 167–170.
78. Bonsch, D.; Lenz, B.; Fiszer, R.; Frieling, H.; Kornhuber, J.; Bleich, S. Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J. Neural Transm. 2006, 113, 1299–1304.
79. Bleich, S.; Lenz, B.; Ziegenbein, M.; Beutler, S.; Frieling, H.; Kornhuber, J.; Bonsch, D. Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence. Alcohol. Clin. Exp. Res. 2006, 30, 587–591.
80. Biermann, T.; Reulbach, U.; Lenz, B.; Frieling, H.; Muschler, M.; Hillemacher, T.; Kornhuber, J.; Bleich, S. N-methyl-D-aspartate 2b receptor subtype (NR2B) promoter methylation in patients during alcohol withdrawal. J. Neural Transm. 2009, 116, 615–622.
81. Philibert, R.A.; Sandhu, H.; Hollenbeck, N.; Gunter, T.; Adams, W.; Madan, A. The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008, 147B, 543–549.
82. Park, B.Y.; Lee, B.C.; Jung, K.H.; Jung, M.H.; Park, B.L.; Chai, Y.G.; Choi, I.G. Epigenetic changes of serotonin transporter in the patients with alcohol dependence: Methylation of an serotonin transporter promoter CpG island. Psychiatry Investig. 2011, 8, 130–133.
83. Lee, B.Y.; Park, S.Y.; Ryu, H.M.; Shin, C.Y.; Ko, K.N.; Han, J.Y.; Koren, G.; Cho, Y.H. Changes in the methylation status of DAT, SERT, and MeCP2 gene promoters in the blood cell in families exposed to alcohol during the periconceptional period. Alcohol. Clin. Exp. Res. 2015, 39, 239–250.
84. Hillemacher, T.; Frieling, H.; Hartl, T.; Wilhelm, J.; Kornhuber, J.; Bleich, S. Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving. J. Psychiatr. Res. 2009, 43, 388–392.
85. Nieratschker, V.; Grosshans, M.; Frank, J.; Strohmaier, J.; von der Goltz, C.; El-Maarri, O.; Witt, S.H.; Cichon, S.; Nothen, M.M.; Kiefer, F.; et al. Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age. Addict. Biol. 2014, 19, 305–311.
86. Jasiewicz, A.; Rubis, B.; Samochowiec, J.; Malecka, I.; Suchanecka, A.; Jablonski, M.; Grzywacz, A. DAT1 methylation changes in alcohol-dependent individuals vs. controls. J. Psychiatr. Res. 2015, 64, 130–133.
87. Ouko, L.A.; Shantikumar, K.; Knezovich, J.; Haycock, P.; Schnugh, D.J.; Ramsay, M. Effect of alcohol consumption on CpG methylation in the differentially methylated regions of H19 and IG-DMR in male gametes—Implications for fetal alcohol spectrum disorders. Alcohol. Clin. Exp. Res. 2009, 33, 1615–1627.
88. Hillemacher, T.; Frieling, H.; Luber, K.; Yazici, A.; Muschler, M.A.; Lenz, B.; Wilhelm, J.; Kornhuber, J.; Bleich, S. Epigenetic regulation and gene expression of vasopressin and atrial natriuretic peptide in alcohol withdrawal. Psychoneuroendocrinology 2009, 34, 555–560.
89. Muschler, M.A.; Hillemacher, T.; Kraus, C.; Kornhuber, J.; Bleich, S.; Frieling, H. DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence. J. Neural Transm. 2010, 117, 513–519.
90. Bayerlein, K.; Kraus, T.; Leinonen, I.; Pilniok, D.; Rotter, A.; Hofner, B.; Schwitulla, J.; Sperling, W.; Kornhuber, J.; Biermann, T. Orexin A A expression and promoter methylation in patients with alcohol dependence comparing acute and protracted withdrawal. Alcohol 2011, 45, 541–547.
91. Heberlein, A.; Muschler, M.; Frieling, H.; Behr, M.; Eberlein, C.; Wilhelm, J.; Groschl, M.; Kornhuber, J.; Bleich, S.; Hillemacher, T. Epigenetic down regulation of nerve growth factor during alcohol withdrawal. Addict. Biol. 2013, 18, 508–510.
92. Hillemacher, T.; Weinland, C.; Lenz, B.; Kraus, T.; Heberlein, A.; Glahn, A.; Muschler, M.A.; Bleich, S.; Kornhuber, J.; Frieling, H. DNA methylation of the LEP gene is associated with craving during alcohol withdrawal. Psychoneuroendocrinology 2015, 51, 371–377.
93. Zhang, H.; Herman, A.I.; Kranzler, H.R.; Anton, R.F.; Simen, A.A.; Gelernter, J. Hypermethylationof OPRM1 promoter region in European Americans with alcohol dependence. J. Hum. Genet. 2012, 57, 670–675.
94. Thapar, M.; Covault, J.; Hesselbrock, V.; Bonkovsky, H.L. DNA methylation patterns in alcoholics and family controls. World J. Gastrointest. Oncol. 2012, 4, 138–144.
95. Zhang, H.; Herman, A.I.; Kranzler, H.R.; Anton, R.F.; Zhao, H.; Zheng, W.; Gelernter, J. Array-based profiling of DNA methylation changes associated with alcohol dependence. Alcohol. Clin. Exp. Res. 2013, 37, E108–E115.
96. Zhang, H.; Wang, F.; Kranzler, H.R.; Zhao, H.; Gelernter, J. Profiling of childhood adversity-associated DNA methylation changes in alcoholic patients and healthy controls. PLoS ONE 2013, 8, e65648.
97. Weng, J.T.; Wu, L.S.; Lee, C.S.; Hsu, P.W.; Cheng, A.T. Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption. Comput. Biol. Med. 2015, 64, 299–306.
98. Zhang, R.; Miao, Q.; Wang, C.; Zhao, R.; Li, W.; Haile, C.N.; Hao, W.; Zhang, X.Y. Genome-wide DNA methylation analysis in alcohol dependence. Addict. Biol. 2013, 18, 392–403.
99. Philibert, R.A.; Plume, J.M.; Gibbons, F.X.; Brody, G.H.; Beach, S.R. The impact of recent alcohol use on genome wide DNA methylation signatures. Front. Genet. 2012, 3, doi:10.3389/fgene.2012.00054.
100. Zhao, R.; Zhang, R.; Li, W.; Liao, Y.; Tang, J.; Miao, Q.; Hao, W. Genome-wide DNA methylation patterns in discordant sib pairs with alcohol dependence. Asia Pac. Psychiatry 2013, 5, 39–50.
101. Philibert, R.A.; Penaluna, B.; White, T.; Shires, S.; Gunter, T.; Liesveld, J.; Erwin, C.; Hollenbeck, N.; Osborn, T. A pilot examination of the genome-wide DNA methylation signatures of subjects entering and exiting short-term alcohol dependence treatment programs. Epigenetics 2014, 9, 1212–1219.
102. Clark, S.L.; Aberg, K.A.; Nerella, S.; Kumar, G.; McClay, J.L.; Chen, W.; Xie, L.Y.; Harada, A.; Shabalin, A.A.; Gao, G.; et al. Combined whole methylome and genomewide association study implicates CNTN4 in alcohol use. Alcohol. Clin. Exp. Res. 2015, 39, 1396–1405.
103. Bonsch, D.; Lenz, B.; Reulbach, U.; Kornhuber, J.; Bleich, S. Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism. J. Neural Transm. 2004, 111, 1611–1616.
104. Zhu, Z.Z.; Hou, L.; Bollati, V.; Tarantini, L.; Marinelli, B.; Cantone, L.; Yang, A.S.; Vokonas, P.; Lissowska, J.; Fustinoni, S.; et al. Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis. Int. J. Epidemiol. 2012, 41, 126–139.
105. Ono, H.; Iwasaki, M.; Kuchiba, A.; Kasuga, Y.; Yokoyama, S.; Onuma, H.; Nishimura, H.; Kusama, R.; Ohnami, S.; Sakamoto, H.; et al. Association of dietary and genetic factors related to one-carbon metabolism with global methylation level of leukocyte DNA. Cancer Sci. 2012, 103, 2159–2164.
106. Ponomarev, I.; Wang, S.; Zhang, L.; Harris, R.A.; Mayfield, R.D. Gene coexpression networks in human brain identify epigenetic modifications in alcohol dependence. J. Neurosci. 2012, 32, 1884–1897.
107. Manzardo, A.M.; Henkhaus, R.S.; Butler, M.G. Global DNA promoter methylation in frontal cortex of alcoholics and controls. Gene 2012, 498, 5–12.
108. Semmler, A.; Heese, P.; Stoffel-Wagner, B.; Muschler, M.; Heberlein, A.; Bigler, L.; Prost, J.C.; Frieling, H.; Kornhuber, J.; Banger, M.; et al. Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: Results from the german investigation on neurobiology in alcoholism (GINA). Alcohol 2015, 49, 97–101.
109. Beach, S.R.H.; Dogan, M.V.; Lei, M.-K.; Cutrona, C.; Gerrard, M.; Gibbons, F.X.; Simons, R.; Brody, G.; Philibert, R. Methylomic aging as a window on lifestyle impact: Tobacco and alcohol use alter the rate of biological aging. J. Am. Gerontol. Assoc. 2015, in press.
110. Patton, G.C.; Coffey, C.; Carlin, J.B.; Sawyer, S.M.; Lynskey, M. Reverse gateways? Frequent cannabis use as a predictor of tobacco initiation and nicotine dependence. Addiction 2005, 100, 1518–1525.
111. Volkow, N. National longitudinal study of the neurodevelopmental consequences of substance use. Available online: http://www.niaaa.nih.gov/news-events/news-noteworthy/nationallongitudinal- study-neurodevelopmental-consequences-substance(accessed on 29 September 2014).
112. McLaren, J.; Swift, W.; Dillon, P.; Allsop, S. Cannabis potency and contamination: A review of the literature. Addiction 2008, 103, 1100–1109.
113. Rotter, A.; Bayerlein, K.; Hansbauer, M.; Weiland, J.; Sperling, W.; Kornhuber, J.; Biermann, T. Orexin A A expression and promoter methylation in patients with cannabis dependence in comparison to nicotine-dependent cigarette smokers and nonsmokers. Neuropsychobiology 2012, 66, 126–133.
114. Rotter, A.; Bayerlein, K.; Hansbauer, M.; Weiland, J.; Sperling, W.; Kornhuber, J.; Biermann, T. CB1 and CB2 receptor expression and promoter methylation in patients with cannabis dependence. Eur. Addict. Res. 2013, 19, 13–20.
115. DiNieri, J.A.; Wang, X.; Szutorisz, H.; Spano, S.M.; Kaur, J.; Casaccia, P.; Dow-Edwards, D.; Hurd, Y.L. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol. Psychiatry 2011, 70, 763–769.
116. Peppin, J.F.; Passik, S.D.; Couto, J.E.; Fine, P.G.; Christo, P.J.; Argoff, C.; Aronoff, G.M.; Bennett, D.; Cheatle, M.D.; Slevin, K.A. Recommendations for urine drug monitoring as a component of opioid therapy in the treatment of chronic pain. Pain Med. 2012, 13, 886–896.
117. Stein, C. Opioid receptors. Annu. Rev. Med. 2015, 67, Epub ahead of print.
118. Nielsen, D.A.; Yuferov, V.; Hamon, S.; Jackson, C.; Ho, A.; Ott, J.; Kreek, M.J. Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts. Neuropsychopharmacology 2009, 34, 867–873.
119. Nielsen, D.A.; Hamon, S.; Yuferov, V.; Jackson, C.; Ho, A.; Ott, J.; Kreek, M.J. Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts. Hum. Genet. 2010, 127, 639–649.
120. McCowan, T.; Dhasarathy, A.; Carvelli, L. The epigenetic mechanisms of amphetamine. J. Addict. Prev. 2015, S(1), 1–7.
121. Schmidt, H.D.; McGinty, J.F.; West, A.E.; Sadri-Vakili, G. Epigenetics and psychostimulant addiction. Cold Spring Harb. Perspect. Med. 2013, 3, doi:10.1101/cshperspect.a012047.
122. Feng, J.; Shao, N.; Szulwach, K.E.; Vialou, V.; Huynh, J.; Zhong, C.; Le, T.; Ferguson, D.; Cahill, M.E.; Li, Y.; et al. Role of Tet1 and 5-hydroxymethylcytosine in cocaine action. Nat. Neurosci. 2015, 18, 536–544.
123. Feng, J.; Nestler, E.J. Epigenetic mechanisms of drug addiction. Curr. Opin. Neurobiol. 2013,23, 521–528.
124. Dedeurwaerder, S.; Defrance, M.; Bizet, M.; Calonne, E.; Bontempi, G.; Fuks, F. A comprehensiveoverview of Infinium HumanMethylation450 data processing. Briefings Bioinform. 2014, 15, 929–941.
125. Zhang, X.; Mu, W.; Zhang, W. On the analysis of the illumina 450k array data: Probes ambiguously mapped to the human genome. Front. Genet. 2012, 3, doi:10.3389/fgene.2012.00073.
126. Price, M.E.; Cotton, A.M.; Lam, L.L.; Farre, P.; Emberly, E.; Brown, C.J.; Robinson, W.P.; Kobor, M.S. Additional annotation enhances potential for biologically-relevant analysis of the illumina Infinium HumanMethylation450 Beadchip array. Epigenet. Chromatin 2013, 6, doi:10.1186/1756-8935-6-4.