What Is the “Environment” in Gene-Environment Interaction Research?

Scene in Brazil. Bill Dressler

The notion that nature and nurture interact to produce the phenotype of an individual is a very old one. Modern techniques of molecular biology and the mapping of the human genome have led to multiple studies approaching gene-environment interaction as more than a metaphor. What is lacking, however, is an adequate conceptualization of “the environment.”

Avshalom Caspi and associates were leaders in gene-environment interaction research in their studies of depression.  They examined a gene linked to the serotonin transporter mechanism, which influences how long the neurotransmitter serotonin remains in the synapse between nerve cells. Caspi and associates found that the condition of individuals possessing a specific polymorphism or gene variant for the serotonin transporter gene and having experienced recent stressful life events increased the risk of depression. For individuals with other gene variants, risk of depression associated with the experience of stressful life events was reduced.

This was revolutionary work that inspired an explosion of papers examining gene-environment interaction, or GxE. It also generated its own controversies and lively debates. One such debate revolves around the question of whether or not GxE effects have been detected at all. First, replication of results in GxE research is highly variable. While there have been many replications of GxE effects, the number of studies failing to replicate is troubling. Second, researchers have severely criticized the “candidate gene” approach, where one gene (or sometimes a multiple polymorphism index) is examined, in favor of an approach involving genome-wide scans. In the genome-wide scan method, respondents are divided into groups who are depressed and not depressed, and then the entire genome for each individual in each group is scanned to see if there is some collection of genes that differ between them.  Supporters of this approach argue that any complex phenotype, like depression, is likely to be the result of multiple—literally dozens—of interacting genes. Candidate gene researchers are finding spurious results, their critics argue, because they are capitalizing on a chance outcome, given the hundreds of possible combinations of genes that could be detected.

The sociocultural context looms large in the overall biocultural process: there is a cultural mediation of a gene-environment interaction, which social class in turn moderates.
While the candidate gene versus genome-wide scan arguments are interesting, what seems more relevant to me is the question raised earlier: what is the “environment” in gene-environment interaction research? As I noted, there has been an explosion of papers in GxE research, and with only a few exceptions, the “environment” examined consists solely of the occurrence of stressful life events. These have been assessed both during childhood (referred to as “childhood adversity”) and as standard concurrent stressful events (e.g., unemployment, death of a close family member); but typically, that’s “the environment.”

Why have GxE researchers stuck to an impoverished view of the human environment? I think because most of them have been more interested in the genes than in the environment (and that is, of course, an important way to proceed). Since a number of researchers have found interesting results employing a measure of experience in the social environment as easy and straightforward as stressful life events, it simplified research design to stick to that. It does, however, leave the environment in GxE work under-specified.

The lack of attention to the environment in these debates make GxE research an area ripe for our attention: if anthropologists know about anything, it is context. And if the environment in GxE research refers to anything, it refers to context. We know that the cultural context within which individuals function can be configured in a myriad of ways. Therefore, it is entirely plausible that the variable replication of results in GxE research is a result of the ways in which the environment changes from one study to the next, in subtle and nuanced ways.

My colleagues and I ventured into this area some years ago when we found, in a small subsample from a larger study in Brazil, an interaction between cultural consonance in family life and a polymorphism in the 2A receptor for serotonin. Cultural consonance is the degree to which individuals are able to effectively enact cultural models in their own beliefs and behaviors. Those individuals with a single variant of the gene, if they had low cultural consonance, reported exceptionally high depressive symptoms; those individuals with that same variant, if they had high cultural consonance, reported exceptionally low depressive symptoms. Persons with other gene variants exhibited the same inverse association of cultural consonance and depressive symptoms, but not as strongly.

While we could not replicate the results in a more representative sample, we did find an interaction between childhood adversity and the 2A receptor polymorphism. Cultural consonance in family life in turn mediated the association of the polymorphism with depression, and the interaction and mediating effects were most pronounced among lower social class respondents.

This results in a model that looks like this:

 

This is a far cry from a simple interaction between life events and a gene. The sociocultural context looms large in the overall biocultural process: there is a cultural mediation of a gene-environment interaction, which social class in turn moderates. However, this approach does not lend itself well to the genome-wide scan, since you would end up having a complex, multiple group comparison instead of comparing two groups.

I won’t argue that more complex models of GxE, specified within a sociocultural context, is the only way to proceed. I only want to emphasize is that this is an important way to proceed, and that biocultural anthropology is uniquely situated to contribute to it.

Bill Dressler is a professor of anthropology at the University of Alabama.

Biocultural Systematics is written by members of the University of Alabama Biocultural Medical Anthropology program.

Post a Comment

Want to comment? Please be aware that only comments from current AAA members will be approved. AN is supported by member dues, so discussions on anthropology-news.org are moderated to ensure that current members are commenting. As with all AN content, comments reflect the views of the person who submitted the comment only. The approval of a comment to go live does not signify endorsement by AN or the AAA.

Commenting Disclaimer

Want to comment? Please be aware that only comments from current AAA members will be approve. AN is supported by member dues, so discussions on anthropology-news.org are moderated to ensure that current members are commenting. As with all AN content, comments reflect the views of the person who submitted the comment only. The approval of a comment to go live does not signify endorsement by AN or the AAA.