COMMENTARIES 32. United Nations Office for Disaster communities. Int J Disaster Risk Reduction. et al. eds. Cambridge, UK, and New York, 36. The One Health Initiative. Available Risk Reduction (UNISDR). Chair’ssummary 2013;4:1---9. NY: Cambridge University Press; 2012. at: http://www.onehealthinitiative.com/ presented at: Fourth Session of the Global 34. Intergovernmental Panel on Cli- 35. United Nations Office for Disaster about.php. Accessed April 22, 2014. Platform for Disaster Risk Reduction; May mate Change (IPCC). Managing the Risks Risk Reduction (UNISDR). Summary of 37. Sustainable Development 2015: advo- 21---23, 2013; Geneva, Switzerland. of Extreme Events and Disasters to Ad- country practices and examples. 2005. cacy toolkit: influencing the post-2015 de- 33. Oxley MC. A “people-centred principles- vance Climate Change Adaption: A Special Available at: http://www.unisdr.org/ velopment agenda. Available at: http://www. based” post-Hyogo framework to Report of Working Groups I and II of the 2005/mdgs-drr/summary-countries.htm. sustainabledevelopment2015.org/index.php/ strengthen the resilience of nations and IPCC. Field CB, Barros V, Stocker TF, Accessed April 24, 2014. about/timeline. Accessed November 1, 2013. Epigenome: Biosensor of Cumulative Exposure to Chemical and Nonchemical Stressors Related to Environmental Justice Understanding differential Kenneth Olden, PhD, ScD, Yu-Sheng Lin, ScD, David Gruber, PhD, and Babasaheb Sonawane, PhD disease susceptibility requires new tools to quantify the PROFOUND HEALTH DISPAR- cumulative effects of envi- between environmental justice community-level environmental fl ronmental stress. Evidence ities exist between af uent Amer- and health disparities, one must justice---related exposures. suggests that social, physical, icans and their socioeconomically develop tools that integrate com- and chemical stressors can disadvantaged and minority coun- munity characteristics, social con- FROM GENOME TO influence disease through terparts.1 A landmark study showed ditions, and cultural influences EPIGENOME the accumulation of epige- that the most significant risk fac- into the risk assessment---risk netic modifications. tors accounting for differential management paradigm. Candidate gene and genome- Geographically stable epi- health outcomes were related to We examine the growing wide association studies have genetic alterations could iden- the environment.2 For example, body of evidence suggesting that identified genetic loci for numer- tify plausible mechanisms for minority communities of color are environmental exposures can in- ous diseases and traits.6 However, health disparities among the exposed to more environmental fluence the development of non- disease mechanisms are complex, disadvantaged and poor. Rela- tions between neighborhood- pollutants than are White com- communicable diseases in human and genetic variations appear to 3 specific epigenetic markers munities because toxic waste populations through the accumu- account directly for only a small fi fi and disease would identify sites, land lls, congested road- lation of chemical modi cations in proportion of disease phenotypes. the most appropriate targets ways, and manufacturing facilities DNA and chromatin that subse- The phenotypic expression of for medical and environmen- are most often located in such quently alter gene expression in specific genes varies with envi- tal intervention. Complex neighborhoods.4 The large and target-specific tissues. Geographic ronmental conditions and has interactions among genes, disproportionate environmental neighborhood-specific epigeneti- been attributed to chemical mod- the environment, and disease burden of the broad array of en- cally stable alterations potentially ification of DNA and chromatin, require the examination of vironmental hazards borne by can be used as platforms to in- collectively known as the epige- how epigenetic changes reg- poor and minority communities, vestigate the mechanisms ac- nome.7---11 Aberrant micro-RNA ulate susceptibility to envi- labeled environmental justice, is counting for well-documented expression also has been associ- ronmental stressors. Progress 12 in understanding disparities likely to be a major contributor to health disparities (as shown sche- ated with disease such as cancer in disease susceptibility may health disparities. matically in Figure 1). By charac- and may represent another form depend on assessing the To date, efforts to link health terizing differential epigenetic of epigenetic regulation of gene cumulative effect of envi- disparities and environmental jus- modifications associated with expression. Epigenetic research, ronmental stressors on ge- tice have been largely observa- living in a “disadvantaged” com- however, has concentrated on netic substrates. tional, and most have focused on pared with an “advantaged” methylation of CpG dinucleotides We highlight key concepts single risk factors. In addition to neighborhood, one can gain within promoter sequences of regarding the interface be- coexposure to multiple chemicals a mechanistic understanding of DNA and chemical modifications tween environmental stress, and physical agents, a large body the relation between environ- (e.g., acetylation) of histones, the epigenetics, and chronic dis- of evidence has emerged indicat- mental justice and health dispar- chief protein component of the ease. (Am J Public Health. ing that social and behavioral ities. Insight into these epigenetic chromatin.13---15 We thus focus 2014;104:1816–1821. doi:10. ’ 2105/AJPH.2014.302130) factors moderate an individual s contributions to health disparities primarily on methylation and response to hazardous environ- could logically lead to action- histones. mental exposures.5 Therefore, to able strategies to reduce hazard- Studies have shown that, in elucidate the complex relation ous exposures and screen for most cases, genetic predisposition 1816 | Commentaries | Peer Reviewed | Olden et al. American Journal of Public Health | October 2014, Vol 104, No. 10 COMMENTARIES Disadvantaged neighborhoods are often exposed to not only chemical agents but also higher Genetics levels of nonchemical stressors, both physical (e.g., noise) and so- Environment cial (e.g., unhealthy food and psy- Physical Chemical chosocial stress).18,38,39 Reports sug- gest that these nonchemical stressors can cause epigenetic Social Behavioral changes,40,41 although this field of study is still in its early stages. For example, maternal care such as grooming and nursing of rat Neighborhood-specific epigenome Biosensors of cumulative exposure pups alters the methylation pro- file within a critical receptor Regulation of gene expression gene in the brain of the pups (e.g., 41 “-omic” biomarkers (e.g., proteomics) hypothalamus). Similarly, mal- fl Phenotype (e.g., dysregulation of β-cell differentiation) treatment, con ict-laden familial relationships, and unhealthy physical and social environments Health disparities (e.g., type 2 diabetes risk) during childhood also can alter the human epigenome in ways that Source. Population image was adopted from Centers for Disease Control and Prevention. Health Disparities and Inequalities Report 2011. influence brain structure and its Available at: http://www.cdc.gov/mmwr. functional plasticity.42 The prena- FIGURE 1—Framework for proposed neighborhood-specific epigenome analysis for the study of tal exposure of the developing environmental health disparities. child to famine (“Dutch Hunger Winter” cohort of 1944---194543) was associated with hypomethyla- creates the potential for adverse contaminated drinking water may alternative pathways for gene--- tion of the key growth factor health outcomes only when sub- be responsible for consistent re- environment interactions capable gene for insulin-like growth factor sequently exposed to environ- ports of higher arsenic and lead of significant effects on human 2(IGF2) and the subsequent mental toxicants16,17; colloquially burdens in racial/ethnic minorities health. Toxic metals such as arse- expression of IGF2. said: “genetics loads the gun, but than in White individuals.19,20 nic and lead can modify disease the environment pulls the trigger.” These exposures raise health con- susceptibility by altering DNA TYPE 2 DIABETES AND For the promise of genomics to cerns because arsenic and lead are methylation and gene expres- CUMULATIVE EPIGENETIC be realized, one must move be- also recognized risk factors for sions.29,30 Indeed, evidence sug- CHANGES yond the discovery of disease- diabetes, cardiovascular and renal gests that the carcinogenicity as- associated genetic variants to disease, and cancer.21--- 2 5 Disad- sociated with these metals results As indicated earlier, populations understanding the epigenetic vantaged communities and popu- from epigenetic modifications.30 living in disadvantaged neighbor- mechanisms by which the envi- lations are also disproportionately Studies also have linked other hoods likely will be compromised ronment may modulate gene ex- exposed to toxic chemicals such environmental chemicals, includ- regarding their capacity both to fi pression and hence trigger disease. as bisphenol A and traf c-related ing bisphenol A and PM2.5, with detoxify chemicals and to methyl- air pollution (e.g., particles with both gene-specific hypermethyla- ate DNA. Once toxicants have NEIGHBORHOOD aerodynamic diameter £ 2.5 lg/m³ tion30---33 and global DNA hypo- entered the body, one mechanism 18,26 fi ENVIRONMENT MATTERS [PM2.5]). methylation (e.g., decreased