Abstract
Evidence emerging from the study of epigenetics and epigenomics challenges notions of health by enhancing understanding of disease etiologies and improving awareness of new health risks. New paradigms arising from epigenetic and epigenomic research present challenging cases through which to debate theories of justice in health because they expand the concept of health and, controversially, place value on what was previously assumed to be ‘healthy' individual variance. Discoveries of the dynamic nature of the epigenome and its variable sensitivity towards change in numerous phenomena add further complexity to the assessment of health inequalities. Such evidence can cast doubt on perceptions of justice in health, which in turn raises questions over the suitability of actions taken in pursuit of equity. This article discusses how recent developments in epigenetics and epigenomics may impact upon assessments of equity in health. A review of literature discussing possible health risks associated with acquired yet heritable epigenetic variance is used to highlight the diversity of possible pathways through which health may be influenced. From this context, the consideration of health risk with respect to epigenetics, it is argued, demands a more inclusive concept of health when used in discussions of inequities.
References
1.
Macinko JA, Starfield B: Annotated bibliography on equity in health, 1980-2001. Int J Equity Health 2002;1:1-20.
2.
Braveman P, Gruskin S: Defining equity in health. J Epidemiol Community Health 2003;57:254-258.
3.
Braveman P: Health disparities and health equity: concepts and measurement. Annu Rev Public Health 2006;27:167-194.
4.
World Health Organization: Basic documents. Constitution of the World Health Organization (47th ed). Geneva, WHO Press, 2009. http://apps.who.int/gb/bd/ (accessed June 18, 2012).
5.
World Health Organization: Comparative quantification of health risks: global and regional burden of disease attributable to selected major risk factors. Geneva, WHO Press, 2004. http://www.who.int/healthinfo/global_burden_disease/cra/en/index.html (accessed June 18, 2012).
6.
World Health Organization: The global burden of disease: 2004 update. Geneva, WHO Press, 2008. http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/index.html (accessed June 18, 2012).
7.
World Health Organization: Noncommunicable diseases: Country profiles 2011. Geneva, WHO Press, 2011. http://www.who.int/nmh/publications/ncd_profiles2011/en/ (accessed June 18, 2012).
8.
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al: The sequence of the human genome. Science 2001;291:1304-1351.
9.
Collins FS, Green ED, Guttmacher AE, Guyer MS; US National Human Genome Research Institute: A vision for the future of genomics research. Nature 2003;422:835-847.
10.
Lunshof JE, Bobe J, Aach J, Angrist M, Thakuria JV, Vorhaus DB, Hoehe MR, Church GM: Personal genomes in progress: from the Human Genome Project to the Personal Genome Project. Dialogues Clin Neurosci 2010:12:47-60.
11.
Jones B: Genomics: personal genome project. Nat Rev Genet 2012;13:599.
12.
Buchanan A, Brock DW, Daniels N, Wikler D: From Chance to Choice: Genetics and Justice. Cambridge, Cambridge University Press, 2000.
13.
Soini S, Ibarreta D, Anastasiadou V, Aymé S, Braga S, Cornel M, Coviello DA, Evers-Kiebooms G, Geraedts J, Gianaroli L, Harper J, Kosztolanyi G, Lundin K, Rodrigues-Cerezo E, Sermon K, Sequeiros J, Tranebjaerg L, Kääriäinen H; ESHG; ESHRE: The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues. Eur J Hum Genet 2006;14:588-645.
14.
Church EM: The personal genome project. Mol Syst Biol 2005;1:2005.0030.
15.
Bialobrzeski A, Ried J, Dabrock P: Differentiating and evaluating common good and public good: making implicit assumptions explicit in the context of consent and duty to participate. Public Health Genomics 2012;15:285-292.
16.
Dabrock P: Meeting the current challenges of governing biobanks responsibly. Public Health Genomics 2012;15:229-231.
17.
Mackenbach JP: Genetics and health inequalities: hypotheses and controversies. J Epidemiol Community Health 2005;59:268-273.
18.
Rothstein MA, Cai Y, Marchant GE: Ethical implications of epigenetics research. Nat Rev Genet 2009;10:224.
19.
Rothstein MA, Cai Y, Marchant GE: The ghost in our genes: legal and ethical implications of epigenetics. Health Matrix Clevel 2009;19:1-62.
20.
Waddington CH: The epigenotype. Endeavour 1942;1:18-20.
21.
Waddington CH: Canalization of development and the inheritance of acquired characteristics. Nature 1942;150:563-565.
22.
Waddington CH: Genetic assimilation of an acquired character. Evolution 1953;7:118-126.
23.
Wolffe AP, Matzke MA: Epigenetics: regulation through repression. Science 1999;286:481-486.
24.
Anway MD, Cupp AS, Uzumcu M, Skinner MK: Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005;308:1466-1469.
25.
Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, Reik W: Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 2003;35:88-93.
26.
Morgan HD, Sutherland HG, Martin DI, Whitelaw E: Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 1999;23:314-318.
27.
Rakyan VK, Chong S, Champ ME, Cuthbert PC, Morgan HD, Luu KVK, Whitelaw E: Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci USA 2003;100:2538-2543.
28.
Callinan PA, Feinberg AP: The emerging science of epigenomics. Hum Mol Genet 2006;15(Spec No 1):R95-R101.
29.
Handel AE, Ebers GC, Ramagopalan SV: Epigenetics: molecular mechansism and implications for disease. Trends Mol Med 2010;16:7-16.
30.
Bernstein BE, Meissner A, Lander ES: The mammalian epigenome. Cell 2007;128:669-681.
31.
Cheng TF, Choudhuri S, Muldoon-Jacobs K: Epigenetic targets of some toxicologically relevant metals: a review of the literature. J App Toxicol 2012;32:643-653.
32.
Mayer W, Niveleau A, Walter J, Fundele R, Haaf T: Embryogenesis: demethylation of the zygotic paternal genome. Nature 2000;403:501-502.
33.
Gorden L, Joo JJ, Powel JE, Ollikainen M, Novakovic B, Li X, Andronikos R, Cruickshank MN, Conneely KN, Smith AK, Alisch RS, Morley R, Visscher PM, Craig JM, Saffery R: Neonatal DNA methylation profile in human twins is specified by a complex intrauterine environmental and genetic factors, subject to tissue-specific influences. Genome Res 2012;22:1395-1406.
34.
Daxinger L, Whitelaw E: Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet 2012;13:153-162.
35.
Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F: RNA-mediated non-mendelian inheritance of an epigenetic change in mouse. Nature 2006;441(7092):469-474.
36.
Wagner KD, Wagner N, Ghanbarian H, Grandjean V, Gounon P, Cuzin F, Rassoulzadegan M: RNA induction and inheritance if epigenetic cardiac hypertrophy in the mouse. Dev Cell 2008;14:962-969.
37.
Wells JCK, Stock JT: Re-examining heritability: genetics, life history and plasticity. Trends Endocrinol Metab 2011;22:421-428.
38.
Bell JT, Spector TD: A twin approach to unraveling epigenetics. Trends Genet 2011;27:116-125.
39.
Feil R, Fraga MF: Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 2012;13:97-109.
40.
Daniels N: Justice, health, and healthcare. Am J Bioeth 2001;1:2-16.
41.
Daniels N: Just Health: Meeting Health Needs Fairly. Cambridge, Cambridge University Press, 2008.
42.
Whitelaw NC, Whitelaw E: Transgenerational epigenetic inheritance in health and disease. Curr Opin Gen Dev 2008;18:273-279.
43.
Jirtle RL, Skinner MK: Environmental epigenomics and disease susceptibility. Nat Rev Genet 2007;8:253-262.
44.
Feinberg AP: Epigenetics at the epicenter of modern medicine. JAMA 2008;299:1345-1350.
45.
Manco M, Dallapiccola B: Genetics of pediatric obesity. Pediatrics 2012;130:123-133.
46.
Hinney A, Vogel CIG, Hebebran J: From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry 2010;19:297-310.
47.
Campión J, Milagro FI, Martínez JA: Individuality and epigenetics in obesity. Obes Rev 2009;10:383-392.
48.
Stöger R: The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes? Bioessays 2008;30:156-166.
49.
Walley AJ, Blakemore AIF, Froguel P: Genetics of obesity and the prediction of risk for health. Hum Mol Genet 2006;15(Spec No 2):R124-R130.
50.
Prescott S, Allen KJ: Food allergy: riding the second wave of the allergy epidemic. Pediatr Allergy Immunol 2011;22:155-160.
51.
Prescott S, Saffery R: The role of epigenetic dysregulation in the epidemic of allergic disease. Clin Epigenetics 2011;2:223-232.
52.
Chang JC, Wang L, Chen RF, Liu CA: Perinatal gene-gene and gene-environment interactions on IgE production and asthma development. Clin Dev Immunol 2012;2012:270869.
53.
Koppelman GH, Nawijn MC: Recent advances in the epigenetics and genomics of asthma. Curr Opin Allergy Clin Immunol 2011;11:414-419.
54.
Ober C, Vercelli D: Gene-environment interactions in human disease: nuisance or opportunity? Trends Genet 2011;27:107-115.
55.
Miller RL, Ho SM: Environmental epigenetics and asthma: current concepts and call for studies. Am J Respir Crit Care Med 2008;177:567-573.
56.
Maric NP, Svrakic DM: Why schizophrenia genetics needs epigenetics: a review. Psychiatr Danub 2012;24:2-18.
57.
Perrin M, Kleinhaus K, Messinger J, Malaspina D: Critical periods and the developmental origins of disease: an epigenetic perspective of schizophrenia. Ann N Y Acad Sci 2010;1204(suppl):E8-E13.
58.
Krebs MO, Bellon A, Mainguy G, Jay TM, Frieling H: One-carbon metabolism and schizophrenia: current challenges and future directions. Trends Mol Med 2009;15:562-570.
59.
Mill J, Petronis A: Pre- and peri-natal environmental risk for attention-deficit hyperactivity disorder (ADHD): the potential role of epigenetic processes in mediating susceptibility. J Child Psychol Psychiatry 2008;49:1020-1030.
60.
Cvekl A, Mitton KP: Epigenetic regulatory mechanisms in vertebrate eye development and disease. Heredity (Edinb) 2010;105:135-151.
61.
Morgan GJ, Alvares CL: Benzene and the hemopoietic stem cell. Chem Biol Interact 2005;153-154:217-222.
62.
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.
63.
Scharl M, Rogler G: Inflammatory bowel disease pathogenesis: what is new? Curr Opin Gastroenterol 2012;28:301-309.
64.
Yehuda R, Flory JD, Pratchett LC, Buxbaum J, Ising M, Holsboer F: Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD. Psychopharmacology 2010;212:405-417.
65.
Butler MG: Genomic imprinting disorders in humans: a mini review. J Assist Reprod Genet 2009;26:477-486.
66.
Bjornsson HT, Fallin MD, Feinberg AP: An integrated epigenetic and genetic approach to common human disease. Trends Genet 2004;20:350-358.
67.
Wallace DC: Bioenergetics and the epigenome: interface between the environment and genes in common diseases. Dev Disabil Res Rev 2010;16:114-119.
68.
Tang W, Ho SM: Epigenetic reprogramming and imprinting in origins of disease. Rev Endocr and Metab Disord 2007;8:173-182.
69.
Ji H, Hershey GKK: Genetic and epigenetic influence on the response to environmental particulate matter. J Allergy Clin Immunol 2012;129:33-41.
70.
Zhang X, Ho SM: Epigenetics meets endocrinology. J Mol Endocrinol 2011;46:R11-R32.
71.
Sutherland JE, Costa M: Epigenetics and the environment. Ann N Y Acad Sci 2003;983:151-160.
72.
Lobanenkov V, Loukinov D, Pugacheva E: Conference scene: environmental epigenomics and disease susceptibility. Epigenomics 2011;3:261-266.
73.
Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, Hanson MA: Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatr Res 2007;61:5R-10R.
74.
Hanson M, Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD: Developmental plasticity and development origins of non-communicable disease: theoretical considerations and epigenetic mechanisms. Prog Biophys Mol Biol 2011;106:272-280.
75.
International Society for Equity in Health: Working definitions. 2001 [N.B. as cited in Macinko and Starfield (2002)].
76.
Whitehead M: The concepts and principles of equity and health. Int J Health Serv 1992;22:429-445.
77.
Peter F: Health equity and social justice. J Appl Philos 2001;18:159-70.
78.
Culyer AJ, Wagstaff A: Equity and equality in health and health care. J Health Econ 1993;12:431-457.
79.
Rawls J: A Theory of Justice. Cambridge, Harvard University Press, 1971.
80.
Boorse C: Health as a theoretical concept. Philos Sci 1977;44:542-573.
81.
Rawls J: Justice as Fairness: A Restatement. Ed. Erin Kelly Cambridge, Harvard University Press, 2001.
82.
Kirk H, Cefalu WT, Ribnicky D, Liu Z, Eilertsen KJ: Botanicals as epigenetic modulators for mechanisms contributing to development of metabolic syndrome. Metabolism 2008;57(7 suppl 1):S16-S23.
83.
Ptak C, Petronis A: Epigenetics and complex diseases: from etiology to new therapeutics. Annu Rev Pharmacol Toxicol 2007;48:257-276.
84.
Zardo G, Cimino G, Nervi C: Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/progenitor cells: therapeutic potential of cell reprogramming. Leukemia 2008;22:1503-1518.
85.
Gorelick R: Neo-Lamarckian medicine. Med Hypotheses 2004;62:299-303.
86.
Szyf M: The dynamic epigenome and its implications in toxicology. Toxicol Sci 2007;100:7-23.
87.
Fish EW, Shahrok D, Bagot R, Caldji C, Bredy T, Szyf M, Meaney MJ: Epigenetic programming of stress responses through variations in maternal care. Ann N Y Acad Sci 2004;1036:167-180.
88.
Skinner MK, Anway MD, Savenkova MI, Gore AC, Crews D: Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior. PLoS One 2008;3:e3745.
89.
Weaver ICG, Cervoni N, Champagne FA, D'Allesio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ: Epigenetic programming by maternal behavior. Nat Neurosci 2004;7:847-854.
90.
Darnaudéry M, Maccari S: Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev 2008;57:571-585.
91.
Weaver ICG: Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: let's call the whole thing off. Epigenetics 2007;2:22-28.
92.
Starfield B: Pathways of influence on equity in health. Soc Sci Med 2007;64:1355-1362.
93.
Robeyns I: The capability approach: a theoretical survey. J Hum Dev 2005;6:93-117.
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