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 authors reference the Dunedin birth cohort study that examined criminal behavior and genetic polymorphisms (the authors specifically reference an MAO A mutation that has been associated with increased criminal behavior). The study demonstrated that among individuals with the particular mutation, those who suffered childhood maltreatment committed a disproportionate amount of the criminal acts in the cohort, whereas those without a history of significant childhood mistreatment committed few criminal acts and the effect of the mutation was eliminated. This suggests that environmental factors influence expression of genes that lead to vastly different phenotypes among individuals with similar genotypes.
Differences in early childhood development and experiences are well known to exist among individuals with different experiences of racism, socioeconomic status, and geographic environments. Considering this and the discussion of the effects of experiences of stress in infancy on the HPA axis (the study of infant rats discussed in the Hertzmann paper), it is reasonable to assume that variable stresses experienced by these different groups contribute to long term health outcomes and the differences we measure among different racial and socioeconomic groups. Considering hypertension, if in early development, humans who do not experience optimal nurturing in response to stress develop higher baseline cortisol levels throughout their lives (as was the case for the young rats), this would lead to higher rates of hypertension among these indiviuals.
In pediatric oncology, it would be interesting to consider carcinogenesis and resiliency throughout treatment among these different groups. We can think of cancer as a particular immunodeficiency, where the immune system (killer T-cells, natural killer cells, and other components) has failed to recognize a malignant cell that is then allowed to divide leading to cancer. It is safe to assume that these different lived experiences and stressors affect immune function, so it is possible that the development of some cancers is impacted by these early life experiences and epigenetic changes. Further, cancer treatment is psychologically and physiologically stressful. During treatment, infections are a significant cause of morbidity and mortality due to immune suppression associated with therapy. If early childhood and other life experiences impact immune function, it is worth considering that some of these patients may be at increased infection risk due to poorer immune function prior to diagnosis. We know that most of the bacterial infections that we treat are from a patient’s own skin or gut flora. If the lived experience affects gene expression, this could impact the microbiome and place patients at risk of infections by different organisms. Finally, survivors of childhood cancer are followed for their long term health outcomes, and it would be interesting to evaluate whether the stress of cancer treatment differentially impacts individuals of different racial and socioeconomic backgrounds. Such differences could be further evidence of the gene by environment interactions influencing health.
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 study of the young rats included in the Hertzmann article discusses cross-generational transmission of epigenetic regulators of brain development. This suggests that some epigenetic changes are heritable, leading directly to impacts on the health of the offspring. Even if the heritability of these genes is not significant, it is likely that individuals with negative health behaviors, baseline stress, and poor stress response influenced by epigenetic changes would be less likely to be able to create am optimally supportive and nurturing environment for their own children. This second hit could lead to similar epigenetic changes in the offspring as in the parents, leading to similar health outcomes and disparities.
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 authors were attempting to evaluate the effect of neighborhood on a patient’s allostatic load which is a measure of physiologic stress that affects multiple health outcomes. The authors were clearly thoughtful when designing their study considering different factors that could mediate or confound the relationship between neighborhood and allostatic load. They considered different objective measures, many of which are commonly measured demographic factors in addition to different health behaviors. Then they considered the individuals’ perception of their neighborhood to measure safety and cohesiveness of the neighborhood. In their analysis, the authors produced a regression model to evaluate the effects of just neighborhood on allostatic load and found an association between poorer neighborhoods and higher allostatic load. However, the authors recognized that there are many other factors that impact and interact with neighborhood income and allostatic load. They developed multiple other models to evaluate different combinations of these factors and their effect on allostatic load. I think most interestingly, the authors were very transparent in their discussion about their reasoning for developing multiple models, and the changes measured in these different models. They describe how in different models, they are able to measure effects from different exposures. It is clear from their study that simply evaluating one measure of socioeconomic status as a surrogate for socioeconomic status as a whole is inadequate and would miss significant factors that mediate relationships between SES and outcome. Further, it demonstrates that broadening the measures included in SES assessment would provide information about specific factors contributing to a particular outcome that could be informative when identifying possible interventions to improve health outcomes.