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.
I agree that gene-by-environment interactions play a major role in chronic disease and their related disparities. Chronic diseases such as obesity may require multiple hits to manifest, such as polygenetic traits that increase obesity susceptibility in addition to environmental exposures such as diet and lack of exercise. Those that have genes or environmental exposures alone may lack the disease phenotype, but together they result in chronic disease. Similarly, hypertension, diabetes, and in turn chronic kidney disease may often require both a genetic susceptibility and environmental factors. A notable example in kidney disease is APOL1, a protein component of HDL. Certain mutations in APOL1 present in those with African ancestry confer resistance against trypanosomiasis (sleeping sickness), but also increase the risk of chronic kidney disease (CKD) and end-stage kidney disease. Approximately 13% of African Americans have APOL1 high risk mutations, but not all these people manifest with kidney disease. Furthermore, APOL1 and environmental factors may not be additive, but rather have effect modification.
2. Discuss implications of epigenetic mechanisms of disease for intergenerational effects on health disparities, as well as for interventions designed to address health disparities.
Heritable epigenetic mechanisms may play a role in intergenerational effects on health disparities. Epigenetic changes that occur during fetal development and childhood are strongly influenced by parental factors, and if these epigenetic changes persist they could manifest in health disparities. For example, children from lower socioeconomic backgrounds are more likely to have stresses during fetal development and have adverse childhood experiences, which may result in epigenetic modifications. For CKD, several epigenetic mechanisms involving inflammation and fibrosis have been described, including methylation, histone modification, and several microRNAs that cause renal fibrosis. The presence of epigenetic mechanisms of disease suggests that these mechanisms should be measured and evaluated in order to fully explain relative disease contribution, and these may need to be accounted for in analyses.
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 Robinette paper constructed 7 scales of allostatic load using 24 physiological indices, that encompassed multiple organ systems. Allostatic load refers to physiologic effects of chronic stress. Their first model finds an association between neighborhood income and allostatic load, independent of income, age, and gender. Model 2 added perceptions of neighborhood safety and neighborhood cohesion to the model (Model 2). Model 3 added perceived stress and symptoms of anxious arousal. Both model 2 and 3 include neighborhood and stress factors which may be confounders in the association between neighborhood income and allostatic load. Model 4 relates to our socioecological model by adding the intermediary factors of health behaviors (tobacco, fast food consumption and exercise). In these ways, the models include community, organizational, and individual factors. They could include further measures of interpersonal interactions such as variables about social support. Other sociodemographic factors beside income, such as education and occupation, could have also been added.