This is one of the first imaging gene-by-environment interaction studies. It provides an example of how incorporating the environment into imaging genetics research can clarify the relationships between genes and brain function (46). Moreover, it has become increasingly evident in imaging genetics that common single genetic polymorphisms are likely to have small effects, if any, on brain function or behavior (2). By incorporating the environment into such models, we may gain traction in demonstrating relationships between these small effects and behaviorally relevant brain function (46). While our entire model accounted for 7% of the variance in threat-related amygdala reactivity, the genotype-by-emotional neglect interaction only accounted for 1.4% of the variance in amygdala reactivity after controlling for main effects of genotype and emotional neglect. This is a relatively small amount of independent variance; however, when viewed in the context of the overall model it still demonstrates significant predictive utility for questions of basic science and, potentially, even those related to clinical issues (e.g., novel molecular targets). For example, studies reporting associations between amygdala reactivity and 5-HTTLPR genotype have accounted for similar
