EPI222_WTR16: Week 5 Assignment

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”?

I do think that this mechanism is relevant in humans. I think there are many ways that parents interact with their children in early developmental periods that has relevance for a wide array of later-life behaviors and capabilities. One analogous concept in humans comes from attachment theory. Secure attachment is predictive of later life success emotionally (relationships), educationally and mentally (self-confidence etc.) Secure attachment is most often established when a child is an infant and is influenced by the caregivers eye contact, tone of voice, response to the child, and most obviously physical contact, among other things. Another analogy is verbal engagement at an early age; studies have shown that parents who speak to their children even before the children can fully understand or reply, raise higher functioning children with better verbal capabilities.

Gruenewald, in contrast, emphasize 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.

I think that they are consistent and both important to our understanding of chronic disease more broadly. The Weaver article discusses epigenetic changes to a particular gene, which has a critical period of susceptibility to environmental effects. Weaver purports that any environmental influence later in the life course is unable or unlikely to modify the gene expression of this receptor. The Gruenewald article discusses cumulative effects of SES adversity, and found that there was a significant (albeit attenuated) effect of early life SES adversity independent of later life. To me this indicates that perhaps the early life window is sensitive to SES but that other exposures later in the lifecourse can partially or fully reverse this effect. I think the Gruenewald approach is more consistent with the broader chronic disease literature, where we know there are windows of susceptibility to exposures but that because diseases have such multi-factorial causes, there are more proximal exposures that can blunt or exacerbate the effects of these earlier life exposures.

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?

I do think that GxE interactions can contribute to our understanding of major disparities. Genetic epidemiology is contributing substantially to our knowledge of both a) what genes or combinations of genes are implicated in chronic disease, and b) the distribution of these genes in our heterogenous population of individuals. The additional step of having good evidence on GxE interaction helps us identify the populations of individuals that should be screened for the important genes, and then provided with the information and opportunity for an intervention to decrease their risk. Because genomes are more similar in people of similar races, I think this is probably an area with the most potential to reduce disparities using GxE, by targeting interventions to those who are most likely to benefit from them. That being said, we need to come a long way farther in our GxE evidence, but I think the potential is definitely there.

Re: Week 5 Assignment

by Maria Glymour - Tuesday, February 2, 2016, 11:02 AM

Nice comments Natalie. The response of social epidemiologists to GxE are somewhat mixed. One perspective on this idea that we can use evidence on GxE to identify people who are especially vulnerable to adverse environments is "why not just protect everyone from adverse environments?" For example, we found that education is especially protective for HbA1c levels among people with high genetic risk of diabetes. So, the "use GxE for screening" perspective would suggest we need to identify people with high genetic risk of diabetes and make sure they attend college. That seems absurd- everyone should have the opportunity to attend college. Same thing if we consider the environment something like maternal nurturing or safe childhoods... even if you have genetic resilience to have a good health outcome despite an adverse childhood environment, you should still not be exposed to an adverse childhood environment.

So what kinds of environmental exposures would we really say should be guided by genetic background? This makes sense when the environment is really a pharmaceutical treatment, ie drug A versus drug B, but when the environment is a larger social context - when does it make sense? I'm not quite sure where the boundaries are here, and I think it's an issue that social inequalities researchers need to struggle with.

One reason I find GxE stories interesting is that they challenge a blame the victim story, the the notion that, because some people have good health despite adverse social environments, everyone could have good health if they were just more determined or did whatever those resilient people do. But I have definitely had social epi people firmly reject my perspective on this and argue GxE research basically takes the emphasis off of the modifiable environmental or social determinants of health.