摘要：Recent research has suggested that the social environment can moderate the expression of genetic influences on health and that genetic influences can shape an individual’s sensitivity to the social environment. Evidence supports 4 major mechanisms: genes can influence an individual’s response to environmental stress, genes may enhance an individual’s sensitivity to both favorable and adverse environments, inherited characteristics may better fit with some environments than with others, and inherited capabilities may only become manifest in challenging or responsive environments. Further progress depends on better recognition of patterns of gene–environment interaction, improved methods of assessing the environment and its impact on genetic mechanisms, the use of appropriately designed laboratory studies, identification of heritable differences in an individual before environmental moderation occurs, and clarification of the timing of the impact of social and genetic moderation. The term gene–environment (G×E) refers either to moderation by genetic influences of the impact of the environment on health or to conditions in which the effect of the genotype on health depends on qualities of the environment. We focus specifically on attributes of the social environment and behavioral health, while recognizing that G×E also encompasses variations in the physical environment (e.g., exposure to allergens or toxins) and a range of public health outcomes. Studies of G×E address a fundamental public health question: Do genetically influenced attributes of individuals make them especially susceptible to adverse social environments or especially responsive to favorable environments (including therapeutic interventions)? Three major research paradigms are available for estimating genetic influences: direct ascertainment of the genotype through molecular assays, twin and sibling studies, and adoption studies. We review evidence from each approach, focusing specifically on the measured social environment. Although questions have been raised about the replicability of some G×E findings, a major question is not simply whether G×E occurs or is pervasive, but how it occurs. We build on a range of previous explorations of these mechanisms. 1–4 First, using published data, we identify 4 broad classes of mechanisms by which genetic and social influences moderate each other: inherited sensitivity to stress in the social environment, differential susceptibility to either favorable or adverse social environments, the goodness of fit between individuals’ inherited dispositions and the attributes of the social environment, and the social enhancement of inherited capabilities. We then identify 2 underlying processes that cut across these 4 mechanisms: genetic variation in the sensitivity to the environment and variation in environmental sensitivity to genetic effects. Finally, we outline 5 steps for exploring specific mechanisms within these classes and link these to prevention and intervention strategies.
