Review: DNA methylation and alcohol use disorders: Progress and challenges

American Journal on Addictions

Volumn 26, Issue 5, 2017, Pages 502-515

  Zhang, Huiping ^a,b   Gelernter, Joel ^a,b  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VA CONNECTICUT HEALTHCARE SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR BETA3; ALCOHOL DEHYDROGENASE 1A; ALCOHOL DEHYDROGENASE 7; ALDEHYDE DEHYDROGENASE 1 FAMILY MEMBER A2; ALDEHYDE DEHYDROGENASE 3B2; ALDEHYDE DEHYDROGENASE ISOENZYME 1; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME A; ARGIPRESSIN; ATRIAL NATRIURETIC FACTOR; CYTOCHROME P450; CYTOCHROME P450 2A13; DNA METHYLTRANSFERASE 3B; DOPAMINE 4 RECEPTOR; DOPAMINE TRANSPORTER; GANGLIOSIDE INDUCED DIFFERENTIATION ASSOCIATED PROTEIN 1; HOMOCYSTEINE INDUCED ENDOPLASMIC RETICULUM PROTEIN; METHYL CPG BINDING PROTEIN; METHYL CPG BINDING PROTEIN 3; MU OPIATE RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; NERVE CELL ADHESION MOLECULE; NERVE CELL ADHESION MOLECULE 1; OREXIN A; PROOPIOMELANOCORTIN; REPETITIVE DNA; SEROTONIN 2B RECEPTOR; SEROTONIN 3A RECEPTOR; SEROTONIN TRANSPORTER; SOMATOSTATIN RECEPTOR 4; UNCLASSIFIED DRUG;

ALCOHOL CONSUMPTION; ALCOHOLISM; DNA METHYLATION; DNA SEQUENCE; DRINKING BEHAVIOR; GENE EXPRESSION; GENETIC SUSCEPTIBILITY; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMAN; HUMAN GENOME; PROMOTER REGION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMATIC REVIEW; GENETICS;

ALCOHOLISM; DNA METHYLATION; HUMANS; PROMOTER REGIONS, GENETIC;

EID: 84995422462     PISSN: 10550496     EISSN: 15210391     Source Type: Journal    
DOI: 10.1111/ajad.12465     Document Type: Review

References (115)

1. Ball D. Addiction science and its genetics. Addiction. 2008; 103:360–367.
2. Kohnke MD. Approach to the genetics of alcoholism: A review based on pathophysiology. Biochem Pharmacol. 2008; 75:160–177.
3. Enoch MA, Goldman D. The genetics of alcoholism and alcohol abuse. Curr Psychiatry Rep. 2001; 3:144–151.
4. Goldman D, Oroszi G, Ducci F. The genetics of addictions: Uncovering the genes. Nat Rev Genet. 2005; 6:521–532.
5. Quillen EE, Chen XD, Almasy L, 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. 2014; 165B:103–110.
6. Gelernter J, Kranzler HR, Sherva R, et al. Genome-wide association study of alcohol dependence: Significant findings in African- and European-Americans including novel risk loci. Mol Psychiatry. 2014; 19:41–49.
7. Baik I, Cho NH, Kim SH, et al. Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men. Am J Clin Nutr. 2011; 93:809–816.
8. Park BL, Kim JW, Cheong HS, et al. Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: From GWAS to replication. Hum Genet. 2013; 132:657–668.
9. Treutlein J, Cichon S, Ridinger M, et al. Genome-wide association study of alcohol dependence. Arch Gen Psychiatry. 2009; 66:773–784.
10. Schumann G, Coin LJ, Lourdusamy A, et al. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proc Natl Acad Sci USA. 2011; 108:7119–7124.
11. Culverhouse RC, Saccone NL, Stitzel JA, et al. Uncovering hidden variance: Pair-wise SNP analysis accounts for additional variance in nicotine dependence. Hum Genet. 2011; 129:177–188.
12. Agrawal A, Bierut LJ. Identifying genetic variation for alcohol dependence. Alcohol Res. 2012; 34:274–281.
13. Renthal W, Nestler EJ. Epigenetic mechanisms in drug addiction. Trends Mol Med. 2008; 14:341–350.
14. Fan L, Bellinger F, Ge YL, et al. Genetic study of alcoholism and novel gene expression in the alcoholic brain. Addict Biol. 2004; 9:11–18.
15. Nadeau JH. The nature of evidence for and against epigenetic inheritance. Genome Biol. 2015; 16:137.
16. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002; 16:6–21.
17. Stevens M, Cheng JB, Li D, et al. Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods. Genome Res. 2013; 23:1541–1553.
18. Ehrlich M, Gama-Sosa MA, Huang LH, et al. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res. 1982; 10:2709–2721.
19. Antequera F, Bird A. Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci USA. 1993; 90:11995–11999.
20. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci USA. 2006; 103:1412–1417.
21. Hatada I, Fukasawa M, Kimura M, et al. Genome-wide profiling of promoter methylation in human. Oncogene. 2006; 25:3059–3064.
22. Kass SU, Pruss D, Wolffe AP. How does DNA methylation repress transcription? Trends Genet. 1997; 13:444–449.
23. Klose RJ, Bird AP. Genomic DNA methylation: The mark and its mediators. Trends Biochem Sci. 2006; 31:89–97.
24. Maunakea AK, Nagarajan RP, Bilenky M, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010; 466:253–257.
25. Nan X, Ng HH, Johnson CA, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998; 393:386–389.
26. Cho KS, Elizondo LI, Boerkoel CF. Advances in chromatin remodeling and human disease. Curr Opin Genet Dev. 2004; 14:308–315.
27. Girardot M, Feil R, Lleres D. Epigenetic deregulation of genomic imprinting in humans: Causal mechanisms and clinical implications. Epigenomics. 2013; 5:715–728.
28. Hsieh TF. Whole-genome DNA methylation profiling with nucleotide resolution. Methods Mol Biol. 2015; 1284:27–40.
29. Delcuve GP, Rastegar M, Davie JR. Epigenetic control. J Cell Physiol. 2009; 219:243–250.
30. Bocker MT, Hellwig I, Breiling A, et al. Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood. 2011; 117:e182–e189.
31. Sutherland JE, Costa M. Epigenetics and the environment. Ann N Y Acad Sci. 2003; 983:151–160.
32. Varley KE, Gertz J, Bowling KM, et al. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013; 23:555–567.
33. Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005; 6:597–610.
34. Starkman BG, Sakharkar AJ, Pandey SC. Epigenetics-beyond the genome in alcoholism. Alcohol Res. 2012; 34:293–305.
35. Harlaar N. Hutchison KE. Alcohol and the methylome: Design and analysis considerations for research using human samples. Drug Alcohol Depend. 2013; 133:305–316.
36. Nieratschker V, Batra A, Fallgatter AJ. Genetics and epigenetics of alcohol dependence. J Mol Psychiatry. 2013; 1:11.
37. Philibert RA, Plume JM, Gibbons FX, et al. The impact of recent alcohol use on genome wide DNA methylation signatures. Front Genet. 2012; 3:54.
38. Zhao R, Zhang R, Li W, et al. Genome-wide DNA methylation patterns in discordant sib pairs with alcohol dependence. Asia Pac Psychiatry. 2013; 5:39–50.
39. Philibert RA, Penaluna B, White T, et al. 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.
40. Manzardo AM, Henkhaus RS, Butler MG. Global DNA promoter methylation in frontal cortex of alcoholics and controls. Gene. 2012; 498:5–12.
41. Wang F, Xu H, Zhao H, et al. DNA co-methylation modules in postmortem prefrontal cortex tissues of European Australians with alcohol use disorders. Sci Rep. 2016; 6:19430.
42. Tycko B. Allele-specific DNA methylation: Beyond imprinting. Human Mol Genet. 2010; 19:R210–220.
43. Kerkel K, Spadola A, Yuan E, et al. Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation. Nat Genet. 2008; 40:904–908.
44. Shoemaker R, Deng J, Wang W, et al. Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. Genome Res. 2010; 20:883–889.
45. Zhang H, Wang F, Kranzler HR, et al. Identification of methylation quantitative trait loci (mQTLs) influencing promoter DNA methylation of alcohol dependence risk genes. Hum Genet. 2014; 133:1093–1104.
46. Taqi MM, Bazov I, Watanabe H, et al. Prodynorphin CpG-SNPs associated with alcohol dependence: Elevated methylation in the brain of human alcoholics. Addict Biol. 2011; 16:499–509.
47. Yaish MW, Peng M, Rothstein SJ. Global DNA methylation analysis using methyl-sensitive amplification polymorphism (MSAP). Methods Mol Biol. 2014; 1062:285–298.
48. Zhu ZZ, Hou L, Bollati V, et al. Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis. Int J Epidemiol. 2012; 41:126–139.
49. Yang AS, Estecio MR, Doshi K, et al. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res. 2004; 32:e38.
50. Bonsch D, Lenz B, Reulbach U, et al. Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm (Vienna). 2004; 111:1611–1616.
51. Kim DS, Kim YH, Lee WK, et al. Effect of alcohol consumption on peripheral blood Alu methylation in Korean men. Biomarkers. 2016; 21:243–248.
52. Zhang FF, Cardarelli R, Carroll J, et al. Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics. 2011; 6:623–629.
53. Ono H, Iwasaki M, Kuchiba A, 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.
54. Unger T, Badoer E, Gareis C, et al. Atrial natriuretic peptide (ANP) as a neuropeptide: Interaction with angiotensin II on volume control and renal sodium handling. Br J Clin Pharmacol. 1990; 30:83S–88S.
55. Kokame K, Agarwala KL, Kato H, et al. Herp a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress. J Biol Chem. 2000; 275:32846–32853.
56. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998; 92:573–585.
57. McLean PJ, Kawamata H, Ribich S, et al. Membrane association and protein conformation of alpha-synuclein in intact neurons. Effect of Parkinson's disease-linked mutations. J Biol Chem. 2000; 275:8812–8816.
58. Hillemacher T, Frieling H, Luber K, et al. Epigenetic regulation and gene expression of vasopressin and atrial natriuretic peptide in alcohol withdrawal. Psychoneuroendocrinology. 2009; 34:555–560.
59. Bruckmann C, Di Santo A, Karle KN, et al. Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome. Epigenetics. 2016; 11:456–463.
60. Bleich S, Lenz B, Ziegenbein M, et al. 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.
61. Zhang H, Herman AI, Kranzler HR, et al. Hypermethylation of OPRM1 promoter region in European Americans with alcohol dependence. J Hum Genet. 2012; 57:670–675.
62. Bonsch D, Lenz B, Kornhuber J, et al. DNA hypermethylation of the alpha synuclein promoter in patients with alcoholism. Neuroreport. 2005; 16:167–170.
63. Hillemacher T, Frieling H, Hartl T, et al. Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving. J Psychiatr Res. 2009; 43:388–392.
64. Wiers CE, Shumay E, Volkow ND, et al. Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism. Transl Psychiatry. 2015; 5:e648.
65. Nieratschker V, Grosshans M, Frank J, et al. Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age. Addict Biol. 2014; 19:305–311.
66. Jasiewicz A, Rubis B, Samochowiec J, et al. DAT1 methylation changes in alcohol-dependent individuals vs. controls. J Psychiatr Res. 2015; 64:130–133.
67. Biermann T, Reulbach U, Lenz B, et al. N-methyl-D-aspartate 2b receptor subtype (NR2B) promoter methylation in patients during alcohol withdrawal. J Neural Transm (Vienna). 2009; 116:615–622.
68. Philibert RA, Gunter TD, Beach SR, et al. MAOA methylation is associated with nicotine and alcohol dependence in women. Am J Med Genet B Neuropsychiatr Genet. 2008; 147B:565–570.
69. Muschler MA, Hillemacher T, Kraus C, et al. DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence. J Neural Transm (Vienna). 2010; 117:513–519.
70. Bayerlein K, Kraus T, Leinonen I, et al. Orexin A expression and promoter methylation in patients with alcohol dependence comparing acute and protracted withdrawal. Alcohol. 2011; 45:541–547.
71. Philibert RA, Sandhu H, Hollenbeck N, et al. 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.
72. Zhang R, Miao Q, Wang C, et al. Genome-wide DNA methylation analysis in alcohol dependence. Addict Biol. 2013; 18:392–403.
73. Harlaar N, Bryan AD, Thayer RE, et al. Methylation of a CpG site near the ALDH1A2 gene is associated with loss of control over drinking and related phenotypes. Alcohol Clin Exp Res. 2014; 38:713–721.
74. Khalid O, Kim JJ, Kim HS, et al. Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells. Stem Cell Res. 2014; 12:791–806.
75. Bonsch D, Lenz B, Fiszer R, et al. Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm (Vienna). 2006; 113:1299–1304.
76. Liu J, Morgan M, Hutchison K, et al. A study of the influence of sex on genome wide methylation. PLoS ONE. 2010; 5:e10028.
77. Huang H, Chen Z, Huang X. Age-adjusted nonparametric detection of differential DNA methylation with case-control designs. BMC Bioinformatics. 2013; 14:86.
78. Nielsen DA, Hamon S, Yuferov V, et al. Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts. Hum Genet. 2010; 127:639–649.
79. Lan X, Cretney EC, Kropp J, et al. Maternal diet during pregnancy induces gene expression and DNA methylation changes in fetal tissues in sheep. Front Genet. 2013; 4:49.
80. Soubry A, Schildkraut JM, Murtha A, et al. Paternal obesity is associated with IGF2 hypomethylation in newborns: Results from a Newborn Epigenetics Study (NEST) cohort. BMC Med. 2013; 11:29.
81. Supic G, Jagodic M, Magic Z. Epigenetics: A new link between nutrition and cancer. Nutr Cancer. 2013; 65:781–792.
82. Tyrka AR, Price LH, Marsit C, et al. Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: Preliminary findings in healthy adults. PLoS ONE. 2012; 7:e30148.
83. Yang BZ, Zhang H, Ge W, et al. Child abuse and epigenetic mechanisms of disease risk. Am J Prev Med. 2013; 44:101–107.
84. Zhang H, Wang F, Kranzler HR, et al. Profiling of childhood adversity-associated DNA methylation changes in alcoholic patients and healthy controls. PLoS ONE. 2013; 8:e65648.
85. Unternaehrer E, Luers P, Mill J, et al. Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Transl Psychiatry. 2012; 2:e150.
86. de Rooij SR, Costello PM, Veenendaal MV, et al. Associations between DNA methylation of a glucocorticoid receptor promoter and acute stress responses in a large healthy adult population are largely explained by lifestyle and educational differences. Psychoneuroendocrinology. 2012; 37:782–788.
87. Lam LL, Emberly E, Fraser HB, et al. Factors underlying variable DNA methylation in a human community cohort. Proc Natl Acad Sci USA. 2012; 109:17253–17260.
88. Zhang D, Cheng L, Badner JA, et al. Genetic control of individual differences in gene-specific methylation in human brain. Am J Hum Genet. 2010; 86:411–419.
89. Gibbs JR, van der Brug MP, Hernandez DG, et al. Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genet. 2010; 6:e1000952.
90. Bell JT, Pai AA, Pickrell JK, et al. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol. 2011; 12:R10.
91. Schalkwyk LC, Meaburn EL, Smith R, et al. Allelic skewing of DNA methylation is widespread across the genome. Am J Hum Genet. 2010; 86:196–212.
92. Yang C, Li C, Kranzler HR, et al. Exploring the genetic architecture of alcohol dependence in African-Americans via analysis of a genomewide set of common variants. Hum Genet. 2013.
93. Laird PW. Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet. 2010; 11:191–203.
94. Stirzaker C, Taberlay PC, Statham AL, et al. Mining cancer methylomes: Prospects and challenges. Trends Genet. 2014; 30:75–84.
95. Smith AK, Kilaru V, Klengel T, et al. DNA extracted from saliva for methylation studies of psychiatric traits: Evidence tissue specificity and relatedness to brain. Am J Med Genet B Neuropsychiatr Genet. 2015; 168B:36–44.
96. Barker JM, Zhang Y, Wang F, et al. Ethanol-induced Htr3a promoter methylation changes in mouse blood and brain. Alcohol Clin Exp Res. 2013; 37:E101–E107.
97. Davies MN, Volta M, Pidsley R, et al. Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol. 2012; 13:R43.
98. Dedova I, Harding A, Sheedy D, et al. The importance of brain banks for molecular neuropathological research: The New South Wales Tissue Resource Centre experience. Int J Mol Sci. 2009; 10:366–384.
99. Alegria-Torres JA, Baccarelli A, Bollati V. Epigenetics and lifestyle. Epigenomics. 2011; 3:267–277.
100. Zhang H, Herman AI, Kranzler HR, et al. Array-based profiling of DNA methylation changes associated with alcohol dependence. Alcohol Clin Exp Res. 2013; 37:E108–115.
101. Ma L, Hu B, Liu Y, et al. Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice. Cell Stem Cell. 2012; 10:455–464.
102. Gupta K, Hardingham GE, Chandran S. NMDA receptor-dependent glutamate excitotoxicity in human embryonic stem cell-derived neurons. Neurosci Lett. 2013; 543:95–100.
103. Xiang Y, Kim KY, Gelernter J, et al. Ethanol upregulates NMDA receptor subunit gene expression in human embryonic stem cell-derived cortical neurons. PLoS ONE. 2015; 10:e0134907.
104. Brennand KJ, Simone A, Jou J, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011; 473:221–225.
105. Kim KY, Hysolli E, Park IH. Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc Natl Acad Sci USA. 2011; 108:14169–14174.
106. Glahn A, Riera Knorrenschild R, Rhein M, et al. Alcohol-induced changes in methylation status of individual CpG sites, and serum levels of vasopressin and atrial natriuretic peptide in alcohol-dependent patients during detoxification treatment. Eur Addict Res. 2014; 20:143–150.
107. Weng JT, Wu LS, Lee CS, et al. Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption. Comput Biol Med. 2015; 64:299–306.
108. Li YF, Langholz B, Salam MT, et al. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005; 127:1232–1241.
109. Rehan VK, Liu J, Naeem E, et al. Perinatal nicotine exposure induces asthma in second generation offspring. BMC Med. 2012; 10:129.
110. Crocq MA. Alcohol, nicotine, caffeine, and mental disorders. Dialogues Clin Neurosci. 2003; 5:175–185.
111. Grant BF, Hasin DS, Chou SP, et al. Nicotine dependence and psychiatric disorders in the United States: Results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry. 2004; 61:1107–1115.
112. Hasin DS, Grant BF. The national epidemiologic survey on alcohol and related conditions (NESARC) waves 1 and 2: Review and summary of findings. Soc Psychiatry Psychiatr Epidemiol. 2015; 50:1609–1640.
113. Grant BF, Goldstein RB, Saha TD, et al. Epidemiology of DSM-5 alcohol use disorder: Results from the national epidemiologic survey on alcohol and related conditions III. JAMA Psychiatry. 2015; 72:757–766.
114. Reinius LE, Acevedo N, Joerink M, et al. Differential DNA methylation in purified human blood cells: Implications for cell lineage and studies on disease susceptibility. PLoS ONE. 2012; 7:e41361.
115. Joubert BR, Felix JF, Yousefi P, et al. DNA methylation in newborns and maternal smoking in pregnancy: Genome-wide consortium meta-analysis. Am J Hum Genet. 2016; 98:680–696.