Gene-Environment Interaction

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Definition

A gene-environment (G-E) interaction refers to the susceptibility of genotypes to different environmental circumstances. In biometrical genetics, it is akin to a statistical interaction such that genetic effects on a phenotype vary as a function of the levels of an environmental variable.

Current Knowledge

Genotype environment interaction refers to changes in the role of genetic factors under different environments. In genetics, this can be visualized as changes in the genetic effect (heritability) on a trait under different environmental conditions (Figs. 1 and 2). In the figures, the evidence of a G-E interaction is that the genetic effect is greater among individuals at the higher end of the environmental measure. Many behaviors and disorders result from the combination of genetic factors and environmental factors, and possibly, their interactions. This has contradicted the early deterministic view of genetics and has opened the door to promising interventions that reduce the risks from genetic predispositions.

Fig. 1

Dichotomous model of gene-environment (G-E) interaction. A simplified example of a dichotomous genotype (i.e., individuals without the genetic risk variant vs. those with the wildtype genotype) and dichotomous environment (low vs. high scores on a risk environment) interaction. The graph shows that genotype increases the odds of contracting a disorder. Additionally, possession of the genetic risk variant increases the odds of the disorder. Furthermore, the genetic risk is increased for individuals who exhibit high scores on the environment measure

Fig. 2

Continuous model of G-E interaction. A complex example of a continuous genotype (i.e., individuals posses either 0, 1, or 2 copies of the risk allele) and ordinal environment (individuals presents with low, medium, high scores on a risk environment) interaction. The graph shows that as the number of risk alleles possessed increases, the odds-ratio of exhibiting the disorder increases. Furthermore, the genetic risk varies as a function of different levels of the environment

Examples of G-E interaction come in various forms. For instance, Phenylketonuria (PKU) is an autosomal recessive disorder characterized by a deficiency in phenylalanine hydroxylase, an enzyme needed to metabolize phenylalanine into tyrosine. The major side effect of this disorder is an accumulation of phenyl pyruvic acid ultimately resulting in mental retardation. One form of treatment has been a diet low on phenylalanine. This environmental intervention prevents the negative side effect of the genetic abnormality.

Unlike monogenic disorders such as PKU, complex disorders such as depression are more difficult when it comes to identifying environments that alter genetic susceptibility. Numerous studies have explored the relationship between the serotonin system, stressful life events, and depression; however, only a handful have identified an interaction. The most notable of these studies was conducted by Caspi et al. (2003) who reported that genetic variants in the promoters of the serotonin transporter gene interacted with stressful life events to influence the risk for major depression. In a meta-analysis of 26 studies, Risch et al. (2009) found no evidence of an interaction across these investigations. While the findings for depression are mixed, these studies are complicated by limitations in association studies (Donnelly 2008), statistical approaches (Eaves 2006), and identifications of “true” environmental risk factors. Over time, more studies of G-E interaction are expected to emerge as the inclusion of environmental measures in genetic designs becomes more commonplace.