1. Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.” To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions? Please consider this both in general and in respect to your particular area of interest.
The concept of “genes by environment” describes how particular allelic susceptibilities (either genomic or epigenomic) may have greater influences on a person’s phenotype depending on their environmental context. In the Herzmann and Boyce article, they give the example of a polymorphism in the promoter region of the MAOA gene is associated with high levels of antisocial behavior in patients with history of maltreatment in childhood, but was virtually absent in those without this exposure history. In the broader context, these types of interactions can lead to disparities along several dimensions, including socioeconomic ones. For example, if genes associated with increased risk of diabetes have a significant interaction with nutrition, i.e. the effects of these genes at raising blood glucose levels are higher in the presence of a high refined carbohydrate diet, then those who are only able to afford these types of diets are going to have a higher risk of diabetes, while those who can afford healthier diets are not affected. This then perpetuates the disparity because those affected by diabetes will have higher healthcare costs, greater risk of disability, and ultimately have lower incomes over time. In the field of sarcoidosis, this “genes by environment” concept likely plays a role in many ways. For example, there are data to suggest that mutations in the mTOR protein, which regulates immune cell activity, could lead to higher likelihood of granuloma formation, which is essential in the disease process. The increased risk conferred by the mTOR mutation may require certain exposures of the immune system to agents that would initiate a granulomatous response. Once the person is exposed, if they have this mutation, they have a higher risk of developing the disease. This exposure may be from a fungal infection, which could be from coccidiodes, which is found in the soil and is associated with farm laborers and inhabitants of certain geographic areas with overall lower incomes. Therefore, those with this mutation could be affected by their occupation and where they live and have an increased risk of developing the disease, and those with the mutation who live and work in areas and occupations with lower likelihood of exposure may be protected. Once a patient is diagnosed with sarcoidosis, it can cause severe debilitating respiratory and fatigue symptoms, which limit their ability to achieve higher income or move. It is unknown what the cause of sarcoidosis is, and more research is needed in what drives persistent granuloma formation, but an interaction between genes and environment is very likely.
2. Discuss implications of epigenetic mechanisms of disease for intergenerational effects on health disparities, as well as for interventions designed to address health disparities.
The transmission of epigenetic modifications from parents to their children occurs both through the genome and through common environmental exposures. Specific alleles can be associated with pathways that ultimately affect which genes are turned on at critical points in development through DNA methylation. The environmental contributions to the transmission of epigenetic traits implies that parents who have specific environmental exposures, e.g. exposure to air pollution because of where they can afford to live, may have epigenetic changes that result in higher likelihood of airway hyperreactivity and asthma. This susceptibility may increase the likelihood of developing asthma and therefore lead to decreased income-earning potential over their lifetime. They may also have other factors, such as race, that lead to their remaining in environments that have negative effects on airway function. They therefore remain in this environment and when they raise their children in the same environment, those same exposures lead to the same epigenetic changes that influence their likelihood of having asthma. The implication of this is that there is a passage of biologically mediated risks for certain diseases that may appear inherent to one’s genome, but actually is environmental. Therefore, unless proper studies are done to determine the role of environmental exposure on the disease, spurious associations may be drawn that link diseases to classifiers like race, when understanding the environmental component could lead to better outcomes by addressing these environmental and socially-determined risk factors.
3. Discuss how the findings in the Robinette paper relate to socioecological model we are using in this course – e.g. briefly describe how the different levels displayed in this model are related to each other in this paper.
The investigators in the Robinette paper attempted to identify multiple levels by which intermediary and individual factors may be associated with greater “allostatic load”, i.e. markers of greater environmental stress/wear and tear that are associated with poorer outcomes. They used census track data to identify the neighborhoods where people lived to identify potential mediators related to geography (e.g. which may be associated to direct availability of resources like supermarkets and outdoor spaces) as well as neighborhood income, neighborhood safety, and neighborhood cohesion. They also measured individual SES (in the form of income) as well as individual health behaviors. They found a statistically significant association between allostatic load and neighborhood income, but their analyses allowed them to determine how other factors such as anxiety and perceptions of safety mediated this primary relationship. Their findings suggest that neighborhood income is associated with allostatic load, but other mediators that may have separate influences, such as anxiety and perception of safety, were also important.