摘要：In this essay, we describe a new era of public health research in which prevention science principles are combined with genomic science to produce gene × intervention (G×I) research. We note the roles of behavioral and molecular genetics in risk and protective mechanisms for drug use and psychopathology among children and adolescents, and the results of first-generation genetically informed prevention trials are reviewed. We also consider the need for second-generation research that focuses on G×I effects on mediators or intermediate processes. This research can be used to further understanding of etiological processes, to identify individual differences in children’s and adolescents’ responses to risk, and to increase the precision of prevention programs. We note the caveats about using genetic data to select intervention participants. MORBIDITY AND MORTALITY from noncommunicable diseases among children and adolescents have risen worldwide, whereas for infectious diseases they have declined. 1 Accordingly, the prevention of noncommunicable causes of childhood and adolescent mortality has risen in importance. Problem behaviors that increase the short- and long-term likelihood of morbidity and mortality are largely preventable. These behaviors include unsafe sex; the use of alcohol, tobacco, and other drugs; and depression and antisocial behavior. 2 Prevention science was established as a discipline more than 30 years ago to mitigate these public health problems. Guided by longitudinal, epidemiological studies that provided an understanding of risk and protective factors relevant to many of these problem behaviors, developmentally appropriate prevention programs were constructed that evince both short- and long-term reductions in behaviors that compromise adolescents’ health. In this essay, we describe a new era of public health research in which the principles of prevention science are combined with genomic science to obtain new insights into the etiology and prevention of adolescent problem behaviors. In the sections that follow, we provide an overview of the roles of behavioral and molecular genetics in the etiology of risk and protective mechanisms, describe the ways in which randomized prevention trials can be used to test etiological hypotheses involving gene × environment interactions (G×E) and gene–environment correlations (rGE), review existing and forthcoming gene × intervention interaction (G×I) research, explain how G×I research can increase the precision of preventive interventions through fostering a greater understanding of nonspecific environmental effects, and offer some caveats about the use of genetic data to select participants for preventive interventions. We provide a glossary of terms that may be unfamiliar to some readers in the box on the following page . Glossary of Terms for Etiological Hypotheses about Child and Adolescent Drug Use and Psychopathology Gene-environment correlations (rGE): rGE occur (1) when genetic factors contribute to individual differences in exposure to positive or negative life events (e.g., when genetically influenced characteristics such as sociability or irritability evoke positive or negative responses from others), or (2) when genetically influenced behavior (such as risk-taking propensities) affects the individual’s choice of environmental experiences. Gene × environment interactions (G×E)a: occur when genetic variation alters an individual’s sensitivity to specific environmental effects or when environmental effects exert differential control by ameliorating or amplifying genetic effects. Indicated interventions: Interventions that target individuals at high risk (such as those exposed to chronic adversities, including poverty and harsh parenting) who do not meet the criteria for a diagnosable disorder. Prevention science: A public health approach to prevention that uses risk and protective mechanisms identified through epidemiological research with target populations as the basis for prevention program content. Quantitative behavioral genetics: The use of naturally occurring variation in the genetic relatedness of family members to identify genetic and environmental contributions to behavior. The most common example is the twin design, in which similarities and differences in identical (monozygotic) and fraternal (dizygotic) twins are compared as a means of estimating genetic and environmental influences. Selective interventions: Interventions that target individuals who have 1 or more risk factors (such as peer drug use or parental depression), but who are not symptomatic (do not themselves use drugs or experience depressive symptoms). Universal interventions: Interventions designed to improve targeted outcomes for everyone in the population, regardless of risk status. Open in a separate window aExamples of G×E effects include specific genotypes’ rendering individuals more susceptible to all experiences, good or bad, and high levels of parental involvement and monitoring decreasing the association of a risk genotype with youth conduct problems and drug use.
