Jessica Enogieru H/W Week 3
- Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life. They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important. Do you think this mechanism is relevant in humans? If so, what behaviors are most analogous to “maternal licking and grooming”?
More often than not, in human beings, parental behavior towards a newborn infant can modulate various phenotypes expressed in the infant in a time sensitive manner. Examples of human parental behavior analogous to “maternal licking and grooming” include maternal skin-to-skin contact (SSC) immediately after birth and SSC during infant and toddler years. Moore and colleagues (PMCID = PMC3979156) performed a meta-analysis of RCTs that evaluated the effects of early SSC on breastfeeding, physiological adaptation, and behavior in healthy newborns. They found infants exposed to early SSC demonstrated a trend toward increased breastfeeding duration. These infants showed statistically better cardio-respiratory stability and higher blood glucose levels.
2. Provide a brief proposal for a study that would allow you to assess whether epigenetic modifications in humans in response to maternal behavior influence subsequent health of the human (feel free to choose any health or behavioral outcome you think you can do this with, e.g., dementia or depression or smoking). Bonus if you can explain how you would approach this if we assume that the relevant epigenetic changes are tissue specific and occur in the brain.
I would propose a prospective long term case-control study that compares ChIP-Seq data of adults exposed to high levels of SSC as a newborn and infant versus adults exposed to low levels of SSC as a newborn and infant. The hypothesis is that adults exposed to low levels of SSC as a newborn and infant would experience higher rates of autoimmune diseases (psoriasis, autoimmune hepatitis) due to a less “matured” and robust immune system from differential expressed epigenetic markers. I would evaluate autoimmune diseases that affect easily biopsied tissues (e.g. skin, liver) so that skin or liver tissue samples could be obtained to perform ChIP-Seq analysis. Chip-Seq data could reveal differential acetylation patterns of histones and differentially methylated DNA in areas of the genome that regulate immune response in various tissues (e.g. MHC, interleukin and cytokine receptor genes). Samples would be collected immediately after birth (as available) and as an adult.
3. Gruenewald, in contrast to Weaver, emphasizes the cumulative effects of SES adversity on a multi-system allostatic load measure. Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings? Explain.
Gruenewalds findings are unrelated to Weavers findings because Weaver’s analysis is specific and focused on determining the epigenetic mechanism of ONE intervention (maternal licking & gromming) that differentially expresses ONE gene (GR). Weaver’s hypothesis and analysis focused on a specific epigenetic mechanism underlying the influences of one environmental change (maternal licking and grooming) on epigenetic markers (histone acetylation and CpG methylation) on binding of one transcription factor (NFasdf) to the promoter of one glucocorticoid receptor gene and plasma cortisone levels. The expression of glucocorticoid receptor and cortisol levels is one of many factors that influences stress response in an animal.
However, Gruenwalds analysis is multifactorial with respect to the intervention (childhood and adult SES parameters combined into one) and the endpoint being studied (AL which is a combination of physiological factors [glucose, lipid, inflammation markers]). Each of the physiological factors that comprise AL, is itself influenced by and interacts with countless other factors.
These two articles are “apples and oranges” with respect to their methodology and endpoints. So one cannot simply compare the two results.
4. 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?
Gene by environment interactions can have a profound effect on health disparities. Gene by environment interactions, as suggested by Weaver, can produce generational effects on offspring. Thus not only is one generation affected, but the subsequent generations to follow. That contributes to the perpetuation and “growth” of the disparity in the future.
Not only can they reveal health disparities along racial or socioeconomic lines but they can also reveal the effect environment has on genes derived from the same population. For example, in the United States African Americans have a significantly higher risk of being diagnosed with primary hypertension compared with other race/ethnic groups. However, when looking at a similar racial group living in a different environment (Africans living in Ghana), the rate of hypertension in Ghana lower than in African Americans in the US. If we adjusted for SES, this difference is most likely due to differences in environmental exposure (more active lifestyle in Ghana, less exposure to processed foods, etc).