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Epigenetics in eating disorders: a systematic review


Eating disorders are complex heritable conditions influenced by both genetic and environmental factors. Given the progress of genomic discovery in anorexia nervosa, with the identification of the first genome-wide significant locus, as well as animated discussion of epigenetic mechanisms in linking environmental factors with disease onset, our goal was to conduct a systematic review of the current body of evidence on epigenetic factors in eating disorders to inform future directions in this area. Following PRISMA guidelines, two independent authors conducted a search within PubMed and Web of Science and identified 18 journal articles and conference abstracts addressing anorexia nervosa (n = 13), bulimia nervosa (n = 6), and binge-eating disorder (n = 1), published between January 2003 and October 2017. We reviewed all articles and included a critical discussion of field-specific methodological considerations. The majority of epigenetic analyses of eating disorders investigated methylation at candidate genes (n = 13), focusing on anorexia and bulimia nervosa in very small samples with considerable sample overlap across published studies. Three studies used microarray-based technologies to examine DNA methylation across the genome of anorexia nervosa and binge-eating disorder patients. Overall, results were inconclusive and were primarily exploratory in nature. The field of epigenetics in eating disorders remains in its infancy. We encourage the scientific community to apply methodologically sound approaches using genome-wide designs including epigenome-wide association studies (EWAS), to increase sample sizes, and to broaden the focus to include all eating disorder types.

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  1. 1.

    Hoek HW. Review of the worldwide epidemiology of eating disorders. Curr Opin Psychiatry. 2016;29:336–9.

    Article  Google Scholar 

  2. 2.

    Ágh T, Kovács G, Supina D, Pawaskar M, Herman BK, Vokó Z, et al. A systematic review of the health-related quality of life and economic burdens of anorexia nervosa, bulimia nervosa, and binge eating disorder. Eat Weight Disord. 2016;21:353–64.

    Article  Google Scholar 

  3. 3.

    Culbert KM, Racine SE, Klump KL. Research review: what we have learned about the causes of eating disorders—a synthesis of sociocultural, psychological, and biological research. J Child Psychol Psychiatry. 2015;56:1141–64.

    Article  Google Scholar 

  4. 4.

    Yilmaz Z, Hardaway JA, Bulik CM. Genetics and epigenetics of eating disorders. Adv Genom Genet. 2015;5:131–50.

    CAS  Google Scholar 

  5. 5.

    Plagnol V, Howson JMM, Smyth DJ, Walker N, Hafler JP, Wallace C, et al. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet. 2011;7:e1002216.

    CAS  Article  Google Scholar 

  6. 6.

    Duncan L, Yilmaz Z, Gaspar H, Walters R, Goldstein J, Anttila V, et al. Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. Am J Psychiatry. 2017;174:850–8.

    Article  Google Scholar 

  7. 7.

    Campbell IC, Mill J, Uher R, Schmidt U. Eating disorders, gene-environment interactions and epigenetics. Neurosci Biobehav Rev. 2011;35:784–93.

    Article  Google Scholar 

  8. 8.

    Steiger H, Thaler L. Eating disorders, gene-environment interactions and the epigenome: roles of stress exposures and nutritional status. Physiol Behav. 2016;162:181–5.

    CAS  Article  Google Scholar 

  9. 9.

    Pjetri E, Schmidt U, Kas MJ, Campbell IC. Epigenetics and eating disorders. Curr Opin Clin Nutr Metab Care. 2012;15:330–5.

    CAS  Article  Google Scholar 

  10. 10.

    Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, et al. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518:317–30.

    Article  Google Scholar 

  11. 11.

    Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.

    CAS  Article  Google Scholar 

  12. 12.

    Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.

    CAS  Article  Google Scholar 

  13. 13.

    Böhmdorfer G, Wierzbicki AT. Control of chromatin structure by long noncoding RNA. Trends Cell Biol. 2015;25:623–32.

    Article  Google Scholar 

  14. 14.

    Hannon E, Dempster E, Viana J, Burrage J, Smith AR, Macdonald R, et al. An integrated genetic-epigenetic analysis of schizophrenia: evidence for co-localization of genetic associations and differential DNA methylation. Genome Biol. 2016;17:176.

    Article  Google Scholar 

  15. 15.

    Aberg KA, McClay JL, Nerella S, Clark S, Kumar G, Chen W, et al. Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults. JAMA Psychiatry. 2014;71:255–64.

    CAS  Article  Google Scholar 

  16. 16.

    De Jager PL, Srivastava G, Lunnon K, Burgess J, Schalkwyk LC, Yu L, et al. Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat Neurosci. 2014;17:1156–63.

    Article  Google Scholar 

  17. 17.

    Lunnon K, Smith R, Hannon E, De Jager PL, Srivastava G, Volta M, et al. Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease. Nat Neurosci. 2014;17:1164–70.

    CAS  Article  Google Scholar 

  18. 18.

    Zhu L, Wang X, Li X-L, Towers A, Cao X, Wang P, et al. Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders. Hum Mol Genet. 2014;23:1563–78.

    Article  Google Scholar 

  19. 19.

    Wong CCY, Meaburn EL, Ronald A, Price TS, Jeffries AR, Schalkwyk LC, et al. Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Mol Psychiatry. 2014;19:495–503.

    CAS  Article  Google Scholar 

  20. 20.

    Globisch D, Münzel M, Müller M, Michalakis S, Wagner M, Koch S, et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS ONE. 2010;5:e15367.

    CAS  Article  Google Scholar 

  21. 21.

    Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324:929–30.

    CAS  Article  Google Scholar 

  22. 22.

    Gibbs JR, van der Brug MP, Hernandez DG, Traynor BJ, Nalls MA, Lai S-L, et al. Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genet. 2010;6:e1000952.

    Article  Google Scholar 

  23. 23.

    McClay JL, Shabalin AA, Dozmorov MG, Adkins DE, Kumar G, Nerella S, et al. High density methylation QTL analysis in human blood via next-generation sequencing of the methylated genomic DNA fraction. Genome Biol. 2015;16:291.

    Article  Google Scholar 

  24. 24.

    Joehanes R, Just AC, Marioni RE, Pilling LC, Reynolds LM, Mandaviya PR, et al. Epigenetic signatures of cigarette smoking. Circ Cardiovasc Genet. 2016;9:436–47.

    CAS  Article  Google Scholar 

  25. 25.

    Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115.

    Article  Google Scholar 

  26. 26.

    Birney E, Smith GD, Greally JM. Epigenome-wide association studies and the interpretation of disease—omics. PLoS Genet. 2016;12:e1006105.

    Article  Google Scholar 

  27. 27.

    Mill J, Heijmans BT. From promises to practical strategies in epigenetic epidemiology. Nat Rev Genet. 2013;14:585–94.

    CAS  Article  Google Scholar 

  28. 28.

    Steinhausen H-C, Jensen CM. Time trends in lifetime incidence rates of first-time diagnosed anorexia nervosa and bulimia nervosa across 16 years in a Danish nationwide psychiatric registry study. Int J Eat Disord. 2015;48:845–50.

    Article  Google Scholar 

  29. 29.

    Volpe U, Tortorella A, Manchia M, Monteleone AM, Albert U, Monteleone P. Eating disorders: what age at onset? Psychiatry Res. 2016;238:225–7.

    Article  Google Scholar 

  30. 30.

    Kesselmeier M, Pütter C, Volckmar A-L, Baurecht H, Grallert H, Illig T, et al. High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation. World J Biol Psychiatry 2018;19: 187–99.

    Article  Google Scholar 

  31. 31.

    Thornton LM, Trace SE, Brownley KA, Ålgars M, Mazzeo SE, Bergin JE, et al. A comparison of personality, life events, comorbidity, and health in monozygotic twins discordant for anorexia nervosa. Twin Res Hum Genet. 2017;20:310–8.

    Article  Google Scholar 

  32. 32.

    Caslini M, Bartoli F, Crocamo C, Dakanalis A, Clerici M, Carrà G. Disentangling the association between child abuse and eating disorders: a systematic review and meta-analysis. Psychosom Med. 2016;78:79–90.

    Article  Google Scholar 

  33. 33.

    Szyf M, Bick J. DNA methylation: a mechanism for embedding early life experiences in the genome. Child Dev. 2013;84:49–57.

    Article  Google Scholar 

  34. 34.

    Provençal N, Binder EB. The effects of early life stress on the epigenome: from the womb to adulthood and even before. Exp Neurol. 2015;268:10–20.

    Article  Google Scholar 

  35. 35.

    Marzi SJ, Sugden K, Arseneault L, Belsky DW, Burrage J, Corcoran DL, et al. Analysis of DNA methylation in young people: limited evidence for an association between victimization stress and epigenetic variation in blood. Am J Psychiatry. 2018;175:517–29.

    Article  Google Scholar 

  36. 36.

    Kular L, Kular S. Epigenetics applied to psychiatry: clinical opportunities and future challenges. Psychiatry Clin Neurosci. 2018;72:195–211.

    Article  PubMed  Google Scholar 

  37. 37.

    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.

    Article  Google Scholar 

  38. 38.

    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.

    Book  Google Scholar 

  39. 39.

    World Health Organization. ICD-10: international statistical classification of diseases and related health problems: 10th revision.. Geneva: World Health Organization; 1992.

    Google Scholar 

  40. 40.

    Ryan R, Hill S. How to GRADE the quality of the evidence. Cochrane Consumers and Communication Group [Internet]. 2016. [cited 2018 Jan 05] Available from:

  41. 41.

    Ramoz N, Guillaume S, Courtet P, Gorwood P. Epigenetics in the remission of anorexia nervosa: a follow-up study of whole- genome methylation profiles. Eur Psychiatry. 2017;41:S102.

    Article  Google Scholar 

  42. 42.

    Frieling H, Bleich S, Otten J, Römer KD, Kornhuber J, de Zwaan M, et al. Epigenetic downregulation of atrial natriuretic peptide but not vasopressin mRNA expression in females with eating disorders is related to impulsivity. Neuropsychopharmacology. 2008;33:2605–9.

    CAS  Article  Google Scholar 

  43. 43.

    Frieling H, Albrecht H, Jedtberg S, Gozner A, Lenz B, Wilhelm J, et al. Elevated cannabinoid 1 receptor mRNA is linked to eating disorder related behavior and attitudes in females with eating disorders. Psychoneuroendocrinology. 2009;34:620–4.

    CAS  Article  Google Scholar 

  44. 44.

    Frieling H, Römer KD, Scholz S, Mittelbach F, Wilhelm J, De Zwaan M, et al. Epigenetic dysregulation of dopaminergic genes in eating disorders. Int J Eat Disord. 2010;43:577–83.

    Article  Google Scholar 

  45. 45.

    Frieling H, Gozner A, Römer KD, Lenz B, Bönsch D, Wilhelm J, et al. Global DNA hypomethylation and DNA hypermethylation of the alpha synuclein promoter in females with anorexia nervosa. Mol Psychiatry. 2007;12:229–30.

    CAS  Article  Google Scholar 

  46. 46.

    Ehrlich S, Weiss D, Burghardt R, Infante-Duarte C, Brockhaus S, Muschler MA, et al. Promoter specific DNA methylation and gene expression of POMC in acutely underweight and recovered patients with anorexia nervosa. J Psychiatr Res. 2010;44:827–33.

    Article  Google Scholar 

  47. 47.

    Ehrlich S, Walton E, Roffman JL, Weiss D, Puls I, Doehler N, et al. Smoking, but not malnutrition, influences promoter-specific DNA methylation of the proopiomelanocortin gene in patients with and without anorexia nervosa. Can J Psychiatry. 2012;57:168–76.

    Article  Google Scholar 

  48. 48.

    Steiger H, Labonté B, Groleau P, Turecki G, Israel M. Methylation of the glucocorticoid receptor gene promoter in bulimic women: associations with borderline personality disorder, suicidality, and exposure to childhood abuse. Int J Eat Disord. 2013;46:246–55.

    Article  Google Scholar 

  49. 49.

    Thaler L, Gauvin L, Joober R, Groleau P, de Guzman R, Ambalavanan A, et al. Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014;54:43–49.

    CAS  Article  Google Scholar 

  50. 50.

    Groleau P, Joober R, Israel M, Zeramdini N, DeGuzman R, Steiger H. Methylation of the dopamine D2 receptor (DRD2) gene promoter in women with a bulimia-spectrum disorder: associations with borderline personality disorder and exposure to childhood abuse. J Psychiatr Res. 2014;48:121–7.

    Article  Google Scholar 

  51. 51.

    Booij L, Casey KF, Antunes JM, Szyf M, Joober R, Israël M, et al. DNA methylation in individuals with anorexia nervosa and in matched normal-eater controls: a genome-wide study. Int J Eat Disord. 2015;48:874–82.

    Article  Google Scholar 

  52. 52.

    Saffrey R, Novakovic B, Wade TD. Assessing global and gene specific DNA methylation in anorexia nervosa: a pilot study. Int J Eat Disord. 2014;47:206–10.

    Article  Google Scholar 

  53. 53.

    Tremolizzo L, Conti E, Bomba M, Uccellini O, Rossi MS, Marfone M, et al. Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents. World J Biol Psychiatry. 2014;15:327–33.

    CAS  Article  Google Scholar 

  54. 54.

    Pjetri E, Dempster E, Collier DA, Treasure J, Kas MJ, Mill J, et al. Quantitative promoter DNA methylation analysis of four candidate genes in anorexia nervosa: a pilot study. J Psychiatr Res. 2013;47:280–2.

    Article  Google Scholar 

  55. 55.

    Kim Y-R, Kim J-H, Kim MJ, Treasure J. Differential methylation of the oxytocin receptor gene in patients with anorexia nervosa: a pilot study. PLoS ONE. 2014;9:e88673.

    Article  Google Scholar 

  56. 56.

    Veldic M, Jia Y-F, Choi Y, Ayers-Ringler JR, Biernacka JM, Geske JR, et al. 450. In bipolar disorder, SLC1A2 promoter hypomethylation is associated with binge eating disorder and nicotine dependance. Biol Psychiatry. 2017;81:S183–S184.

    Article  Google Scholar 

  57. 57.

    Jia Y-F, Choi Y, Ayers-Ringler JR, Biernacka JM, Geske JR, Lindberg DR, et al. Differential SLC1A2 promoter methylation in bipolar disorder with or without addiction. Front Cell Neurosci. 2017;11:217.

    Article  Google Scholar 

  58. 58.

    Kurdyukov S, Bullock M. DNA methylation analysis: choosing the right method. Biology. 2016.

    Article  Google Scholar 

  59. 59.

    Tsai P-C, Bell JT. Power and sample size estimation for epigenome-wide association scans to detect differential DNA methylation. Int J Epidemiol. 2015;44:1429–41.

    Article  Google Scholar 

  60. 60.

    Ligthart S, Marzi C, Aslibekyan S, Mendelson MM, Conneely KN, Tanaka T, et al. DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases. Genome Biol. 2016;17:255.

    Article  Google Scholar 

  61. 61.

    ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.

    Article  Google Scholar 

  62. 62.

    Stunnenberg HG, International Human Epigenome Consortium, Hirst M. The International Human Epigenome Consortium: a blueprint for scientific collaboration and discovery. Cell. 2016;167:1145–9.

    CAS  Article  Google Scholar 

  63. 63.

    Leek JT, Scharpf RB, Bravo HC, Simcha D, Langmead B, Johnson WE, et al. Tackling the widespread and critical impact of batch effects in high-throughput data. Nat Rev Genet. 2010;11:733–9.

    CAS  Article  Google Scholar 

  64. 64.

    Sun Z, Chai HS, Wu Y, White WM, Donkena KV, Klein CJ, et al. Batch effect correction for genome-wide methylation data with Illumina Infinium platform. BMC Med Genom. 2011;4:84.

    CAS  Article  Google Scholar 

  65. 65.

    Noble WS. How does multiple testing correction work? Nat Biotechnol. 2009;27:1135–7.

    CAS  Article  Google Scholar 

  66. 66.

    Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Methodol. 1995;57:289–300.

    Google Scholar 

  67. 67.

    Davies MN, Volta M, Pidsley R, Lunnon K, Dixit A, Lovestone S, et al. Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol. 2012;13:R43.

    CAS  Article  Google Scholar 

  68. 68.

    Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013;341:1237905.

    Article  Google Scholar 

  69. 69.

    Ziller MJ, Edri R, Yaffe Y, Donaghey J, Pop R, Mallard W, et al. Dissecting neural differentiation regulatory networks through epigenetic footprinting. Nature. 2015;518:355–9.

    CAS  Article  Google Scholar 

  70. 70.

    Marzi SJ, Meaburn EL, Dempster EL, Lunnon K, Paya-Cano JL, Smith RG, et al. Tissue-specific patterns of allelically-skewed DNA methylation. Epigenetics. 2016;11:24–35.

    Article  Google Scholar 

  71. 71.

    Hannon E, Lunnon K, Schalkwyk L, Mill J. Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes. Epigenetics. 2015;10:1024–32.

    Article  Google Scholar 

  72. 72.

    Jones MJ, Moore SR, Kobor MS. Principles and challenges of applying epigenetic epidemiology to psychology. Annu Rev Psychol. 2018;69:459–85.

    Article  Google Scholar 

  73. 73.

    Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem. 2012;23:853–9.

    CAS  Article  Google Scholar 

  74. 74.

    Paul B, Barnes S, Demark-Wahnefried W, Morrow C, Salvador C, Skibola C, et al. Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases. Clin Epigenetics. 2015;7:112.

    Article  Google Scholar 

  75. 75.

    Mathers JC, Strathdee G, Relton CL. Induction of epigenetic alterations by dietary and other environmental factors. Adv Genet. 2010;71:3–39.

    Article  Google Scholar 

  76. 76.

    Choi S-W, Friso S. Epigenetics: a new bridge between nutrition and health. Adv Nutr. 2010;1:8–16.

    CAS  Article  Google Scholar 

  77. 77.

    Canani RB, Costanzo MD, Leone L, Bedogni G, Brambilla P, Cianfarani S, et al. Epigenetic mechanisms elicited by nutrition in early life. Nutr Res Rev. 2011;24:198–205.

    CAS  Article  Google Scholar 

  78. 78.

    Himmerich H, Treasure J. Psychopharmacological advances in eating disorders. Expert Rev Clin Pharmacol. 2018;11:95–108.

    CAS  Article  Google Scholar 

  79. 79.

    Schorr M, Miller KK. The endocrine manifestations of anorexia nervosa: mechanisms and management. Nat Rev Endocrinol. 2017;13:174–86.

    CAS  Article  Google Scholar 

  80. 80.

    Klump KL, Culbert KM, Sisk CL. Sex differences in binge eating: gonadal hormone effects across development. Annu Rev Clin Psychol. 2017;13:183–207.

    Article  Google Scholar 

  81. 81.

    Csoka AB, Szyf M. Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology. Med Hypotheses. 2009;73:770–80.

    CAS  Article  Google Scholar 

  82. 82.

    Relton CL, Davey Smith G. Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol. 2012;41:161–76.

    Article  Google Scholar 

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Dr. Bulik acknowledges funding from the Swedish Research Council (VR Dnr: 538-2013-8864). This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We gratefully thank the artist Vinícius Gaio, London, UK, for the design of Figure 1.

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Correspondence to Cynthia M. Bulik.

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Dr. Bulik reports: Shire (grant recipient, Scientific Advisory Board member) and Pearson and Walker (author, royalty recipient) (unrelated to the content of this manuscript). Dr. Breen has received grant funding from and served as a consultant to Eli Lilly and has received honoraria from Illumina (all unrelated to the content of this manuscript). The remaining authors declare that they have no conflict of interest.

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Hübel, C., Marzi, S.J., Breen, G. et al. Epigenetics in eating disorders: a systematic review. Mol Psychiatry 24, 901–915 (2019).

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