摘要：Researchers have proposed a genetic differential sensitivity to social environmental (GDSE) model positing that individuals with certain genetic makeups are more sensitive to favorable and unfavorable environmental influences than those without these genetic makeups. We discuss several issues facing researchers who want to use GDSE to examine health: (1) the need for greater theorizing about the social environment to properly understand the size and direction of environmental influences; (2) the potential for combining multiple genetic markers to measure an individual’s genetic sensitivity to environmental influence; (3) how this model and exogenous shocks deal with gene–environment correlations; (4) implications of this model for public health and prevention; and (5) how life course and developmental theories may be used to inform GDSE research. Studies of human molecular genetics and social environment interactions have increased dramatically during the past decade. 1 Although the majority of these studies rely on a classic diathesis-stress model that emphasizes genetic variations and social environments that are unfavorable or risky, researchers have proposed a differential susceptibility or biological sensitivity model, which postulates that individuals vary in their sensitivity to environments, with those having more genetic sensitivity experiencing more negative outcomes in unfavorable environments and more positive outcomes in favorable environments compared with those having less genetic sensitivity. 1-4 A third model referred to as the social distinction model mirrors the diathesis-stress model by arguing that in the harshest environments outcomes are confined to a narrow range because the environment overwhelms any specific biological pathway. However, given a more supportive environment, the variance of outcomes is larger and that variance is partly caused by genetic factors. Interestingly, little research examines this model, even less than is found for differential susceptibility or biological sensitivity. 5,6 Early research primarily focused on behavioral indicators of sensitivity (negative emotional reactivity to psychosocial challenges or what was sometimes termed difficult temperament) and physiological responses to such challenges (autonomic, immune, and cortisol changes). 7 Interest expanded from considering susceptibility to negative environments to a consideration of sensitivity to positive environments as well. With advances in genotyping, researchers are now using measured gene variations as markers of individuals’ biological sensitivity, creating what we term the genetic differential sensitivity to social environment model (GDSE). In addition to hypothesizing a crossover effect, GDSE models imply that heterogeneity of response to environments (including social interventions, treatments, and policies) may be partly genetic. For this reason, GDSE models can be an important tool not only for understanding population health but also for designing public health policies and programs that are more targeted and more effective. Our goal for this article is to discuss some of the broader theoretical and methodological issues confronting researchers who are using or plan to use GDSE models to enrich their understanding of population health. Others have more formally documented the process of detecting a genuine GDSE model; therefore, we do not review that process here. 3,8 Our first section is a brief review of the 2 theoretical approaches to GDSE. 1–4,7,9–11 In subsequent sections, we discuss the importance of developing positive measures of both environments and health; the advantages and disadvantages of using multiple indicators of the same genetic construct; how the GDSE model and exogenous environmental events can help social scientists to deal with causality; and how GDSE approaches may be useful for public health and prevention. We close with a discussion of the importance of integrating GDSE models with developmental and life course frameworks to further research and prevention efforts.
