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Epigenetics and Chronic Diseases: An Overview

  • Rebecca Smith
  • Jonathan Mill
Chapter

Abstract

According to the World Health Organization, chronic diseases account for an estimated 35 million deaths per year, representing ∼60% of worldwide mortality.163 These disorders, including heart disease, obesity, arthritis, cancer, diabetes, psychiatric illness and dementia, confer a major economic, social, and healthcare burden. In the developed world, for example, the treatment of chronic disease accounts for the major proportion of public healthcare spending. As demographic factors shift and the population ages, the prevalence of chronic disease is likely to increase significantly, especially in the developing world. For instance, the prevalence of adult obesity is on a dramatic upward trajectory, increasing from 12% in 1989 to 27% in 2008 in the USA (http://www.cdc.gov/brfss/). Likewise, as the population ages, the number of cases of Alzheimer’s Disorder is projected to increase from an estimated 24 million in 2001 to >80 million by 2040, with rates in countries such as India and China increasing by more than 300% over this period.41 The possibility of understanding the biology underpinning human chronic illness is therefore one of the most exciting perspectives of contemporary biomedical research, and the focus of considerable research effort across the world.

Keywords

Histone Modification Chronic Fatigue Syndrome Epigenetic Change Twin Pair Epigenetic Process 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Adamo KB, Tesson F. Gene–environment interaction and the metabolic syndrome.Novartis Found Symp. 2008;293:103-119; discussion 119-127.PubMedCrossRefGoogle Scholar
  2. 2.
    Aho K, Koskenvuo M, Tuominen J, Kaprio J. Occurrence of rheumatoid arthritis in a nationwide series of twins.J Rheumatol. 1986;13:899-902.PubMedGoogle Scholar
  3. 3.
    Akbarian S, Huang HS. Epigenetic regulation in human brain-focus on histone lysine methylation.Biol Psychiatry. 2009;65:198-203.PubMedCrossRefGoogle Scholar
  4. 4.
    Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.Nat Genet. 1999;23:185-188.PubMedCrossRefGoogle Scholar
  5. 5.
    Avner P, Heard E. X-chromosome inactivation: counting, choice and initiation.Nat Rev Genet. 2001;2:59-67.PubMedCrossRefGoogle Scholar
  6. 6.
    Balch C, Fang F, Matei DE, Huang TH, Nephew KP. Minireview: epigenetic changes in ovarian cancer.Endocrinology. 2009;150:4003-4011.PubMedCrossRefGoogle Scholar
  7. 7.
    Ballestar E, Ballestar E. Epigenetics lessons from twins: prospects for autoimmune disease.Clin Rev Allergy Immunol. 2010;39(1):30-41.PubMedCrossRefGoogle Scholar
  8. 8.
    Barker DJ. In utero programming of chronic disease.Clin Sci (Lond). 1998;95:115-128.CrossRefGoogle Scholar
  9. 9.
    Barnes PJ, Adcock IM, Ito K. Histone acetylation and deacetylation: importance in inflammatory lung diseases.Eur Respir J. 2005;25:552-563.PubMedCrossRefGoogle Scholar
  10. 10.
    Barnes PJ, Ito K, Adcock IM. Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase.Lancet. 2004;363:731-733.PubMedCrossRefGoogle Scholar
  11. 11.
    Berger SL. The complex language of chromatin regulation during transcription.Nature. 2007;447:407-412.PubMedCrossRefGoogle Scholar
  12. 12.
    Bestor TH. The DNA methyltransferases of mammals.Hum Mol Genet. 2000;9:2395-2402.PubMedCrossRefGoogle Scholar
  13. 13.
    Bird AP. CpG-rich islands and the function of DNA methylation.Nature. 1986;321:209-213.PubMedCrossRefGoogle Scholar
  14. 14.
    Bjornsson HT, Sigurdsson MI, Fallin MD, et al. Intra-individual change over time in DNA methylation with familial clustering.Jama. 2008;299:2877-2883.PubMedCrossRefGoogle Scholar
  15. 15.
    Blewitt ME, Vickaryous NK, Hemley SJ, et al. An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse.Proc Natl Acad Sci U S A. 2005;102:7629-7634.PubMedCrossRefGoogle Scholar
  16. 16.
    Byrne M, Agerbo E, Ewald H, Eaton WW, Mortensen PB. Parental age and risk of schizophrenia: a case-control study.Arch Gen Psychiatry. 2003;60:673-678.PubMedCrossRefGoogle Scholar
  17. 17.
    Caspi A, Sugden K, Moffitt TE, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene.Science. 2003;301:386-389.PubMedCrossRefGoogle Scholar
  18. 18.
    Castle DJ, Wessely S, Murray RM. Sex and schizophrenia: effects of diagnostic stringency, and associations with and premorbid variables.Br J Psychiatry. 1993;162:658-664.PubMedCrossRefGoogle Scholar
  19. 19.
    Chakrabarti SK, Francis J, Ziesmann SM, Garmey JC, Mirmira RG. Covalent histone modifications underlie the developmental regulation of insulin gene transcription in pancreatic beta cells.J Biol Chem. 2003;278:23617-23623.PubMedCrossRefGoogle Scholar
  20. 20.
    Chang HS, Anway MD, Rekow SS, Skinner MK. Transgenerational epigenetic imprinting of the male germline by endocrine disruptor exposure during gonadal sex determination.Endocrinology. 2006;147:5524-5541.PubMedCrossRefGoogle Scholar
  21. 21.
    Chen J, Odenike O, Rowley JD. Leukaemogenesis: more than mutant genes.Nat Rev Cancer. 2010;10:23-36.PubMedCrossRefGoogle Scholar
  22. 22.
    Christensen BC, Houseman EA, Marsit CJ, et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context.PLoS Genet. 2009;5:e1000602.PubMedCrossRefGoogle Scholar
  23. 23.
    Cibelli JB, Campbell KH, Seidel GE, West MD, Lanza RP. The health profile of cloned animals.Nat Biotechnol. 2002;20:13-14.PubMedCrossRefGoogle Scholar
  24. 24.
    Connor CM, Akbarian S. DNA methylation changes in schizophrenia and bipolar disorder.Epigenetics. 2008;3:55-58.PubMedCrossRefGoogle Scholar
  25. 25.
    Cooney CA, Dave AA, Wolff GL. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring.J Nutr. 2002;132:2393S-2400S.PubMedGoogle Scholar
  26. 26.
    Currenti SA. Understanding and determining the etiology of autism.Cell Mol Neurobiol. 2010;30:161-171.PubMedCrossRefGoogle Scholar
  27. 27.
    Davies W, Isles AR, Wilkinson LS. Imprinted gene expression in the brain.Neurosci Biobehav Rev. 2005;29:421-430.PubMedCrossRefGoogle Scholar
  28. 28.
    De Marzo AM, Platz EA, Sutcliffe S, et al. Inflammation in prostate carcinogenesis.Nat Rev Cancer. 2007;7:256-269.PubMedCrossRefGoogle Scholar
  29. 29.
    Deapen D, Escalante A, Weinrib L, et al. A revised estimate of twin concordance in systemic lupus erythematosus.Arthritis Rheum. 1992;35:311-318.PubMedCrossRefGoogle Scholar
  30. 30.
    Dolinoy DC, Jirtle RL. Environmental epigenomics in human health and disease.Environ Mol Mutagen. 2008;49:4-8.PubMedCrossRefGoogle Scholar
  31. 31.
    Dolinoy DC, Weidman JR, Jirtle RL. Epigenetic gene regulation: linking early developmental environment to adult disease.Reprod Toxicol. 2007;23:297-307.PubMedCrossRefGoogle Scholar
  32. 32.
    Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.Environ Health Perspect. 2006;114:567-572.PubMedCrossRefGoogle Scholar
  33. 33.
    Duffy DL, Martin NG, Battistutta D, Hopper JL, Mathews JD. Genetics of asthma and hay fever in Australian twins.Am Rev Respir Dis. 1990;142:1351-1358.PubMedGoogle Scholar
  34. 34.
    Ebers GC, Sadovnick AD. The role of genetic factors in multiple sclerosis susceptibility.J Neuroimmunol. 1994;54:1-17.PubMedCrossRefGoogle Scholar
  35. 35.
    Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy.Nature. 2004;429:457-463.PubMedCrossRefGoogle Scholar
  36. 36.
    Ekstrom TJ, Stenvinkel P. The epigenetic conductor: a genomic orchestrator in chronic kidney disease complications?J Nephrol. 2009;22:442-449.PubMedGoogle Scholar
  37. 37.
    Faire UD, Pedersen N. Studies of twins and adoptees in coronary heart disease. In: Goldbourt U, Faire UD, Berg K, eds.Genetic Factors in Coronary Heart Disease. New York: Springer; 1994:55-68.CrossRefGoogle Scholar
  38. 38.
    Feinberg AP. Phenotypic plasticity and the epigenetics of human disease.Nature. 2007;447:433-440.PubMedCrossRefGoogle Scholar
  39. 39.
    Ferguson-Smith A, Lin SP, Tsai CE, Youngson N, Tevendale M. Genomic imprinting – insights from studies in mice.Semin Cell Dev Biol. 2003;14:43-49.PubMedCrossRefGoogle Scholar
  40. 40.
    Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study.Lancet. 2005;366:2112-2117.PubMedCrossRefGoogle Scholar
  41. 41.
    Flanagan JM, Popendikyte V, Pozdniakovaite N, et al. Intra- and interindividual epigenetic variation in human germ cells.Am J Hum Genet. 2006;79:67-84.PubMedCrossRefGoogle Scholar
  42. 42.
    Flint J. Implications of genomic imprinting for psychiatric genetics.Psychol Med. 1992;22:5-10.PubMedCrossRefGoogle Scholar
  43. 43.
    Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins.Proc Natl Acad Sci U S A. 2005;102:10604-10609.PubMedCrossRefGoogle Scholar
  44. 44.
    Frans EM, Sandin S, Reichenberg A, Lichtenstein P, Langstrom N, Hultman CM. Advancing paternal age and bipolar disorder.Arch Gen Psychiatry. 2008;65:1034-1040.PubMedCrossRefGoogle Scholar
  45. 45.
    Fu M, Rao M, Wang C, et al. Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth.Mol Cell Biol. 2003;23:8563-8575.PubMedCrossRefGoogle Scholar
  46. 46.
    Fu M, Wang C, Zhang X, Pestell RG. Acetylation of nuclear receptors in cellular growth and apoptosis.Biochem Pharmacol. 2004;68:1199-1208.PubMedCrossRefGoogle Scholar
  47. 47.
    Gartner K. A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals?Lab Anim. 1990;24:71-77.PubMedCrossRefGoogle Scholar
  48. 48.
    Gershon ES, Badner JA, Detera-Wadleigh SD, Ferraro TN, Berrettini WH. Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar illness pedigrees.Am J Med Genet. 1996;67:202-207.PubMedCrossRefGoogle Scholar
  49. 49.
    Gluckman PD, Hanson MA. Developmental origins of disease paradigm: a mechanistic and evolutionary perspective.Pediatr Res. 2004;56:311-317.PubMedCrossRefGoogle Scholar
  50. 50.
    Gluckman PD, Hanson MA, Beedle AS. Early life events and their consequences for later disease: a life history and evolutionary perspective.Am J Hum Biol. 2007;19:1-19.PubMedCrossRefGoogle Scholar
  51. 51.
    Gluckman PD, Hanson MA, Buklijas T, Low FM, Beedle AS. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases.Nat Rev Endocrinol. 2009;5:401-408.PubMedCrossRefGoogle Scholar
  52. 52.
    Grant PA, Berger SL. Histone acetyltransferase complexes.Semin Cell Dev Biol. 1999;10:169-177.PubMedCrossRefGoogle Scholar
  53. 53.
    Grewal SI, Jia S. Heterochromatin revisited.Nat Rev Genet. 2007;8:35-46.PubMedCrossRefGoogle Scholar
  54. 54.
    Guo SW. Epigenetics of endometriosis.Mol Hum Reprod. 2009;15:587-607.PubMedCrossRefGoogle Scholar
  55. 55.
    Haque FN, Gottesman II, Wong AH. Not really identical: epigenetic differences in monozygotic twins and implications for twin studies in psychiatry.Am J Med Genet C Semin Med Genet. 2009;151C:136-141.PubMedCrossRefGoogle Scholar
  56. 56.
    Hatchwell E, Greally JM. The potential role of epigenomic dysregulation in complex human disease.Trends Genet. 2007;23:588-595.PubMedCrossRefGoogle Scholar
  57. 57.
    Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans.Proc Natl Acad Sci U S A. 2008;105:17046-17049.PubMedCrossRefGoogle Scholar
  58. 58.
    Henikoff S, Matzke MA. Exploring and explaining epigenetic effects.Trends Genet. 1997;13:293-295.PubMedCrossRefGoogle Scholar
  59. 59.
    Hewagama A, Richardson B. The genetics and epigenetics of autoimmune diseases.J Autoimmun. 2009;33:3-11.PubMedCrossRefGoogle Scholar
  60. 60.
    Imagawa K, de Andes MC, Hashimoto K, Itoi E, Oreffo R, Roach H. Reduced Expression of Collagen Type IX in Human Osteoarthritic Chondrocytrs is Associated with Epigenetic Silencing by DNA Hypermethylation. Osteoarthritis and Cartilage. 2009;18(Suppl. 2):S36-S36.Google Scholar
  61. 61.
    Issa JP, Garcia-Manero G, Giles FJ, et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies.Blood. 2004;103:1635-1640.PubMedCrossRefGoogle Scholar
  62. 62.
    Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals.Nat Genet. 2003;33(Suppl):245-254.PubMedCrossRefGoogle Scholar
  63. 63.
    Javierre BM, Fernandez AF, Richter J, et al. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus.Genome Res. 2010;20:170-179.PubMedCrossRefGoogle Scholar
  64. 64.
    Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility.Nat Rev Genet. 2007;8:253-262.PubMedCrossRefGoogle Scholar
  65. 65.
    Jones PA, Baylin SB. The epigenomics of cancer.Cell. 2007;128:683-692.PubMedCrossRefGoogle Scholar
  66. 66.
    Kalsi G, Prescott CA, Kendler KS, Riley BP. Unraveling the molecular mechanisms of alcohol dependence.Trends Genet. 2009;25:49-55.PubMedCrossRefGoogle Scholar
  67. 67.
    Kaminsky Z, Wang SC, Petronis A. Complex disease, gender and epigenetics.Ann Med. 2006;38:530-544.PubMedCrossRefGoogle Scholar
  68. 68.
    Kaminsky ZA, Tang T, Wang SC, et al. DNA methylation profiles in monozygotic and dizygotic twins.Nat Genet. 2009;41:240-245.PubMedCrossRefGoogle Scholar
  69. 69.
    Kanner L. Autistic disturbances of affective contact.Acta Paedopsychiatr. 1968;35:100-136.PubMedGoogle Scholar
  70. 70.
    Kaprio J, Tuomilehto J, Koskenvuo M, et al. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland.Diabetologia. 1992;35:1060-1067.PubMedCrossRefGoogle Scholar
  71. 71.
    Karouzakis E, Gay RE, Gay S, Neidhart M. Epigenetic control in rheumatoid arthritis synovial fibroblasts.Nat Rev Rheumatol. 2009;5:266-272.PubMedCrossRefGoogle Scholar
  72. 72.
    Karrasch S, Holz O, Jorres RA. Aging and induced senescence as factors in the pathogenesis of lung emphysema.Respir Med. 2008;102:1215-1230.PubMedCrossRefGoogle Scholar
  73. 73.
    Kawakami K, Ruszkiewicz A, Bennett G, et al. DNA hypermethylation in the normal colonic mucosa of patients with colorectal cancer.Br J Cancer. 2006;94:593-598.PubMedCrossRefGoogle Scholar
  74. 74.
    Kinyamu HK, Archer TK. Modifying chromatin to permit steroid hormone receptor-dependent transcription.Biochim Biophys Acta. 2004;1677:30-45.PubMedCrossRefGoogle Scholar
  75. 75.
    Klar AJ. Propagating epigenetic states through meiosis: where Mendel’s gene is more than a DNA moiety.Trends Genet. 1998;14:299-301.PubMedCrossRefGoogle Scholar
  76. 76.
    Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators.Trends Biochem Sci. 2006;31:89-97.PubMedCrossRefGoogle Scholar
  77. 77.
    Kolevzon A, Gross R, Reichenberg A. Prenatal and perinatal risk factors for autism: a review and integration of findings.Arch Pediatr Adolesc Med. 2007;161:326-333.PubMedCrossRefGoogle Scholar
  78. 78.
    Kong A, Steinthorsdottir V, Masson G, et al. Parental origin of sequence variants associated with complex diseases.Nature. 2009;462:868-874.PubMedCrossRefGoogle Scholar
  79. 79.
    Krishnan V, Nestler EJ. The molecular neurobiology of depression.Nature. 2008;455:894-902.PubMedCrossRefGoogle Scholar
  80. 80.
    Lai JC, Cheng YW, Chiou HL, Wu MF, Chen CY, Lee H. Gender difference in estrogen receptor alpha promoter hypermethylation and its prognostic value in non-small cell lung cancer.Int J Cancer. 2005;117:974-980.PubMedCrossRefGoogle Scholar
  81. 81.
    Lin E, Hsu SY. A Bayesian approach to gene-gene and gene-environment interactions in chronic fatigue syndrome.Pharmacogenomics. 2009;10:35-42.PubMedCrossRefGoogle Scholar
  82. 82.
    Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 A resolution.Nature. 1997;389:251-260.PubMedCrossRefGoogle Scholar
  83. 83.
    Macfarlane AJ, Strom A, Scott FW. Epigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes.Mamm Genome. 2009;20(9–10):624-632.PubMedCrossRefGoogle Scholar
  84. 84.
    Maciejewska-Rodrigues H, Karouzakis E, Strietholt S, et al. Epigenetics and rheumatoid arthritis: the role of SENP1 in the regulation of MMP-1 expression.J Autoimmun. 2010;35(1):15-22.PubMedCrossRefGoogle Scholar
  85. 85.
    Maciejewska HR, Jungel A, Gay RE, Gay S. Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis.Mol Immunol. 2009;47:12-18.CrossRefGoogle Scholar
  86. 86.
    Malaspina D, Harlap S, Fennig S, et al. Advancing paternal age and the risk of schizophrenia.Arch Gen Psychiatry. 2001;58:361-367.PubMedCrossRefGoogle Scholar
  87. 87.
    Mani ST, Thakur MK. In the cerebral cortex of female and male mice, amyloid precursor protein (APP) promoter methylation is higher in females and differentially regulated by sex steroids.Brain Res. 2006;1067:43-47.PubMedCrossRefGoogle Scholar
  88. 88.
    Mastroeni D, McKee A, Grover A, Rogers J, Coleman PD. Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease.PloS One. 2009;4:e6617.PubMedCrossRefGoogle Scholar
  89. 89.
    McGowan PO, Kato T. Epigenetics in mood disorders.Environ Health Prev Med. 2008;13:16-24.PubMedCrossRefGoogle Scholar
  90. 90.
    McGowan PO, Sasaki A, D’Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.Nat Neurosci. 2009;12:342-348.PubMedCrossRefGoogle Scholar
  91. 91.
    Meijlink FC, Philipsen JN, Gruber M, Ab G. Methylation of the chicken vitellogenin gene: influence of estradiol administration.Nucleic Acids Res. 1983;11:1361-1373.PubMedCrossRefGoogle Scholar
  92. 92.
    Melki JR, Vincent PC, Clark SJ. Concurrent DNA hypermethylation of multiple genes in acute myeloid leukemia.Cancer Res. 1999;59:3730-3740.PubMedGoogle Scholar
  93. 93.
    Mill J, Dempster E, Caspi A, Williams B, Moffitt T, Craig I. Evidence for monozygotic twin (MZ) discordance in methylation level at two CpG sites in the promoter region of the catechol-O-methyltransferase (COMT) gene.Am J Med Genet B Neuropsychiatr Genet. 2006;141B:421-425.PubMedCrossRefGoogle Scholar
  94. 94.
    Mill J, Petronis A. Molecular studies of major depressive disorder: the epigenetic perspective.Mol Psychiatry. 2007;12(9):799-814.PubMedCrossRefGoogle Scholar
  95. 95.
    Mill J, Petronis A. The relevance of epigenetics to major psychosis. In: Ferguson-Smith A, Greally J, Martienssen R, eds.Epigenomics. New York: Springer; 2009.Google Scholar
  96. 96.
    Mill J, Tang T, Kaminsky Z, et al. Epigenomic profiling reveals DNA methylation changes associated with major psychosis.Am J Hum Genet. 2008;82(3):696-711.PubMedCrossRefGoogle Scholar
  97. 97.
    Miller RL, Ho SM. Environmental epigenetics and asthma: current concepts and call for studies.Am J Respir Crit Care Med. 2008;177:567-573.PubMedCrossRefGoogle Scholar
  98. 98.
    Nagarajan RP, Patzel KA, Martin M, et al. MECP2 promoter methylation and X chromosome inactivation in autism.Autism Res. 2008;1:169-178.PubMedCrossRefGoogle Scholar
  99. 99.
    Ober C, Thompson EE. Rethinking genetic models of asthma: the role of environmental modifiers.Curr Opin Immunol. 2005;17:670-678.PubMedCrossRefGoogle Scholar
  100. 100.
    Ooi SL, Henikoff S. Germline histone dynamics and epigenetics.Curr Opin Cell Biol. 2007;19:257-265.PubMedCrossRefGoogle Scholar
  101. 101.
    Orton SM, Herrera BM, Yee IM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study.Lancet Neurol. 2006;5:932-936.PubMedCrossRefGoogle Scholar
  102. 102.
    Paulsen M, Ferguson-Smith AC. DNA methylation in genomic imprinting, development, and disease.J Pathol. 2001;195:97-110.PubMedCrossRefGoogle Scholar
  103. 103.
    Pembrey ME, Bygren LO, Kaati G, et al. Sex-specific, male-line transgenerational responses in humans.Eur J Hum Genet. 2006;14:159-166.PubMedCrossRefGoogle Scholar
  104. 104.
    Perrin MC, Brown AS, Malaspina D. Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia.Schizophr Bull. 2007;33:1270-1273.PubMedCrossRefGoogle Scholar
  105. 105.
    Petel-Galil Y, Benteer B, Galil YP, et al. Comprehensive diagnosis of Rett’s syndrome relying on genetic, epigenetic and expression evidence of deficiency of the methyl-CpG-binding protein 2 gene: study of a cohort of Israeli patients.J Med Genet. 2006;43:e56.PubMedCrossRefGoogle Scholar
  106. 106.
    Petronis A. Human morbid genetics revisited: relevance of epigenetics.Trends Genet. 2001;17:142-146.PubMedCrossRefGoogle Scholar
  107. 107.
    Petronis A. Epigenetics and bipolar disorder: new opportunities and challenges.Am J Med Genet C Semin Med Genet. 2003;123:65-75.CrossRefGoogle Scholar
  108. 108.
    Petronis A. The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis.Biol Psychiatry. 2004;55:965-970.PubMedCrossRefGoogle Scholar
  109. 109.
    Pidsley R, Dempster EL, Mill J. Brain weight in males is correlated with DNA methylation at IGF2.Mol Psychiatry. 2010;15(9):880-881.PubMedCrossRefGoogle Scholar
  110. 110.
    Plomin R, Owen MJ, McGuffin P. The genetic basis of complex human behaviors.Science. 1994;264:1733-1739.PubMedCrossRefGoogle Scholar
  111. 111.
    Polesskaya OO, Aston C, Sokolov BP. Allele C-specific methylation of the 5-HT2A receptor gene: evidence for correlation with its expression and expression of DNA methylase DNMT1.J Neurosci Res. 2006;83:362-373.PubMedCrossRefGoogle Scholar
  112. 112.
    Preis JI, Downes M, Oates NA, Rasko JE, Whitelaw E. Sensitive flow cytometric analysis reveals a novel type of parent-of-origin effect in the mouse genome.Curr Biol. 2003;13:955-959.PubMedCrossRefGoogle Scholar
  113. 113.
    Quddus J, Johnson KJ, Gavalchin J, et al. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice.J Clin Invest. 1993;92:38-53.PubMedCrossRefGoogle Scholar
  114. 114.
    Rakyan V, Whitelaw E. Transgenerational epigenetic inheritance.Curr Biol. 2003;13:R6.PubMedCrossRefGoogle Scholar
  115. 115.
    Rakyan VK, Blewitt ME, Druker R, Preis JI, Whitelaw E. Metastable epialleles in mammals.Trends Genet. 2002;18:348-351.PubMedCrossRefGoogle Scholar
  116. 116.
    Reynolds E. Vitamin B12, folic acid, and the nervous system.Lancet Neurol. 2006;5:949-960.PubMedCrossRefGoogle Scholar
  117. 117.
    Richards EJ. Inherited epigenetic variation – revisiting soft inheritance.Nat Rev Genet. 2006;7:395-401.PubMedCrossRefGoogle Scholar
  118. 118.
    Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis.Arthritis Rheum. 1990;33:1665-1673.PubMedCrossRefGoogle Scholar
  119. 119.
    Riggs AD, Xiong Z, Wang L, LeBon JM. Methylation dynamics, epigenetic fidelity and X chromosome structure.Novartis Found Symp. 1998;214:214-225; discussion 225-232.PubMedGoogle Scholar
  120. 120.
    Roach HI, Aigner T. DNA methylation in osteoarthritic chondrocytes: a new molecular target.Osteoarthr Cartil. 2007;15:128-137.PubMedCrossRefGoogle Scholar
  121. 121.
    Roach HI, Yamada N, Cheung KS, et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions.Arthritis Rheum. 2005;52:3110-3124.PubMedCrossRefGoogle Scholar
  122. 122.
    Robertson KD, Wolffe AP. DNA methylation in health and disease.Nat Rev Genet. 2000;1(1):11-19.Google Scholar
  123. 123.
    Robinson RL, Carpenter D, Halsall PJ, et al. Epigenetic allele silencing and variable penetrance of malignant hyperthermia susceptibility.Br J Anaesth. 2009;103:220-225.PubMedCrossRefGoogle Scholar
  124. 124.
    Rollins RA, Haghighi F, Edwards JR, et al. Large-scale structure of genomic methylation patterns.Genome Res. 2006;16:157-163.PubMedCrossRefGoogle Scholar
  125. 125.
    Rosa A, Picchioni MM, Kalidindi S, et al. Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins.Am J Med Genet B Neuropsychiatr Genet. 2008;147B:459-462.PubMedCrossRefGoogle Scholar
  126. 126.
    Saha RN, Pahan K. HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis.Cell Death Differ. 2006;13:539-550.PubMedCrossRefGoogle Scholar
  127. 127.
    Saluz HP, Jiricny J, Jost JP. Genomic sequencing reveals a positive correlation between the kinetics of strand-specific DNA demethylation of the overlapping estradiol/glucocorticoid-receptor binding sites and the rate of avian vitellogenin mRNA synthesis.Proc Natl Acad Sci U S A. 1986;83:7167-7171.PubMedCrossRefGoogle Scholar
  128. 128.
    Sandovici I, Kassovska-Bratinova S, Loredo-Osti JC, et al. Interindividual variability and parent of origin DNA methylation differences at specific human Alu elements.Hum Mol Genet. 2005;14:2135-2143.PubMedCrossRefGoogle Scholar
  129. 129.
    Sarter B, Long TI, Tsong WH, Koh WP, Yu MC, Laird PW. Sex differential in methylation patterns of selected genes in Singapore.Chinese Hum Genet. 2005;117:402-403.CrossRefGoogle Scholar
  130. 130.
    Scarpa S, Cavallaro RA, D’Anselmi F, Fuso A. Gene silencing through methylation: an epigenetic intervention on Alzheimer disease.J Alzheimers Dis. 2006;9:407-414.PubMedGoogle Scholar
  131. 131.
    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.PubMedCrossRefGoogle Scholar
  132. 132.
    Schulz WA, Hoffmann MJ. Epigenetic mechanisms in the biology of prostate cancer.Semin Cancer Biol. 2009;19:172-180.PubMedCrossRefGoogle Scholar
  133. 133.
    Schwartz DA. Gene-environment interactions and airway disease in children.Pediatrics. 2009;123(Suppl 3):S151-S159.PubMedCrossRefGoogle Scholar
  134. 134.
    Shen Y, Chow J, Wang Z, Fan G. Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells.Hum Mol Genet. 2006;15:2623-2635.PubMedCrossRefGoogle Scholar
  135. 135.
    Shimabukuro M, Jinno Y, Fuke C, Okazaki Y. Haloperidol treatment induces tissue- and sex-specific changes in DNA methylation: a control study using rats.Behav Brain Funct. 2006;2:37.PubMedCrossRefGoogle Scholar
  136. 136.
    Shimabukuro M, Sasaki T, Imamura A, et al. Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: a potential link between epigenetics and schizophrenia.J Psychiatr Res. 2007;41(12):1042-1046.PubMedCrossRefGoogle Scholar
  137. 137.
    Siegmund KD, Connor CM, Campan M, et al. DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons.PloS One. 2007;2:e895.PubMedCrossRefGoogle Scholar
  138. 138.
    Sipos A, Rasmussen F, Harrison G, et al. Paternal age and schizophrenia: a population based cohort study.BMJ. 2004;329:1070.PubMedCrossRefGoogle Scholar
  139. 139.
    Smith RG, Kember RL, Mill J, et al. Advancing paternal age is associated with deficits in social and exploratory behaviors in the offspring: a mouse model.PloS One. 2009;4:e8456.PubMedCrossRefGoogle Scholar
  140. 140.
    Spencer VA, Davie JR. Role of covalent modifications of histones in regulating gene expression.Gene. 1999;240:1-12.PubMedCrossRefGoogle Scholar
  141. 141.
    St Clair D, Xu M, Wang P, et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959-1961.JAMA. 2005;294:557-562.PubMedCrossRefGoogle Scholar
  142. 142.
    Stenvinkel P, Karimi M, Johansson S, et al. Impact of inflammation on epigenetic DNA methylation – a novel risk factor for cardiovascular disease?J Intern Med. 2007;261:488-499.PubMedCrossRefGoogle Scholar
  143. 143.
    Surani MA, Sasaki H, Ferguson-Smith AC, et al. The inheritance of germline-specific epigenetic modifications during development.Philos Trans R Soc Lond. 1993;339:165-172.CrossRefGoogle Scholar
  144. 144.
    Susser E, Neugebauer R, Hoek HW, et al. Schizophrenia after prenatal famine. Further evidence.Arch Gen Psychiatry. 1996;53:25-31.PubMedCrossRefGoogle Scholar
  145. 145.
    Susser ES, Lin SP. Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944–1945.Arch Gen Psychiatry. 1992;49:983-988.PubMedCrossRefGoogle Scholar
  146. 146.
    Szyf M, Weaver I, Meaney M. Maternal care, the epigenome and phenotypic differences in behavior.Reprod Toxicol. 2007;24(1):9-19.Google Scholar
  147. 147.
    Szulakowski P, Crowther AJ, Jimenez LA, et al. The effect of smoking on the transcriptional regulation of lung inflammation in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2006;174:41-50.PubMedCrossRefGoogle Scholar
  148. 148.
    Takami N, Osawa K, Miura Y, et al. Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells.Arthritis Rheum. 2006;54:779-787.PubMedCrossRefGoogle Scholar
  149. 149.
    Tamashiro KL, Wakayama T, Yamazaki Y, et al. Phenotype of cloned mice: development, behavior, and physiology.Exp Biol Med (Maywood). 2003;228:1193-1200.Google Scholar
  150. 150.
    Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention.Exp Neurol. 2007;208:1-25.PubMedCrossRefGoogle Scholar
  151. 151.
    Thompson NP, Driscoll R, Pounder RE, Wakefield AJ. Genetics versus environment in inflammatory bowel disease: results of a British twin study.BMJ. 1996;312:95-96.PubMedCrossRefGoogle Scholar
  152. 152.
    Tiemann-Boege I, Navidi W, Grewal R, et al. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect.Proc Natl Acad Sci U S A. 2002;99:14952-14957.PubMedCrossRefGoogle Scholar
  153. 153.
    Trenkmann M, Brock M, Ospelt C, Gay S. Epigenetics in rheumatoid arthritis.Clin Rev Allergy Immunol. 2010;39(1):10-19.PubMedCrossRefGoogle Scholar
  154. 154.
    Ushijima T, Watanabe N, Okochi E, Kaneda A, Sugimura T, Miyamoto K. Fidelity of the methylation pattern and its variation in the genome.Genome Res. 2003;13:868-874.PubMedCrossRefGoogle Scholar
  155. 155.
    Wang SC, Oelze B, Schumacher A. Age-specific epigenetic drift in late-onset Alzheimer’s disease.PloS One. 2008;3:e2698.PubMedCrossRefGoogle Scholar
  156. 156.
    Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis.Annu Rev Nutr. 2007;27:363-388.PubMedCrossRefGoogle Scholar
  157. 157.
    Weaver IC, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior.Nat Neurosci. 2004;7:847-854.PubMedCrossRefGoogle Scholar
  158. 158.
    Weaver IC, Meaney MJ, Szyf M. Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood.Proc Natl Acad Sci U S A. 2006;103:3480-3485.PubMedCrossRefGoogle Scholar
  159. 159.
    Widschwendter M, Jiang G, Woods C, et al. DNA hypomethylation and ovarian cancer biology.Cancer Res. 2004;64:4472-4480.PubMedCrossRefGoogle Scholar
  160. 160.
    Wilks A, Seldran M, Jost JP. An estrogen-dependent demethylation at the 5′ end of the chicken vitellogenin gene is independent of DNA synthesis.Nucleic Acids Res. 1984;12:1163-1177.PubMedCrossRefGoogle Scholar
  161. 161.
    Wilks AF, Cozens PJ, Mattaj IW, Jost JP. Estrogen induces a demethylation at the 5′ end region of the chicken vitellogenin gene.Proc Natl Acad Sci U S A. 1982;79:4252-4255.PubMedCrossRefGoogle Scholar
  162. 162.
    Wong AH, Gottesman II, Petronis A. Phenotypic differences in genetically identical organisms: the epigenetic perspective.Hum Mol Genet. 2005;14(Spec No 1):R11-R18.PubMedCrossRefGoogle Scholar
  163. 163.
    World Health O (2005) Preventing chronic diseases: a vital investment.Google Scholar
  164. 164.
    Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW. Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis.Am J Obstet Gynecol. 2005;193:371-380.PubMedCrossRefGoogle Scholar
  165. 165.
    Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis.Fertil Steril. 2007;87:24-32.PubMedCrossRefGoogle Scholar
  166. 166.
    Xu L, Glass CK, Rosenfeld MG. Coactivator and corepressor complexes in nuclear receptor function.Curr Opin Genet Dev. 1999;9:140-147.PubMedCrossRefGoogle Scholar
  167. 167.
    Yauk C, Polyzos A, Rowan-Carroll A, et al. Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location.Proc Natl Acad Sci U S A. 2008;105:605-610.PubMedCrossRefGoogle Scholar
  168. 168.
    Yu J, Zhang H, Gu J, et al. Methylation profiles of thirty four promoter-CpG islands and concordant methylation behaviours of sixteen genes that may contribute to carcinogenesis of astrocytoma.BMC Cancer. 2004;4:65.PubMedCrossRefGoogle Scholar
  169. 169.
    Zammit S, Allebeck P, Dalman C, et al. Paternal age and risk for schizophrenia.Br J Psychiatry. 2003;183:405-408.PubMedCrossRefGoogle Scholar
  170. 170.
    Zawia NH, Lahiri DK, Cardozo-Pelaez F. Epigenetics, oxidative stress, and Alzheimer disease.Free Radic Biol Med. 2009;46:1241-1249.PubMedCrossRefGoogle Scholar
  171. 171.
    Zhou H, Brockington M, Jungbluth H, et al. Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.Am J Hum Genet. 2006;79:859-868.PubMedCrossRefGoogle Scholar

Copyright information

© Springer London 2011

Authors and Affiliations

  1. 1.Institute of PsychiatryKing’s College LondonLondonUK

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