Genetic differential susceptibility on trial: Meta-analytic support from randomized controlled experiments

Abstract

The most stringent test of differential susceptibility theory is provided by randomized control trials examining the moderating role of genetic markers of differential susceptibility in experimental manipulations of the environment (Gene × Experimental Environment interactions), being at least 10 times more powerful than correlational Gene × Environment interaction studies. We identified 22 experiments involving 3,257 participants with various developmental outcomes (e.g., externalizing problems, internalizing behaviors, and cognitive development). Effect sizes contrasting experimental versus control group were computed both for subjects with the polymorphism considered indicative of heightened susceptibility (e.g., the dopamine receptor D4 gene seven-repeat allele and the serotonin transporter polymorphic region short allele) and others expected to be low in susceptibility (e.g., the dopamine receptor D4 gene four-repeat allele and the serotonin transporter polymorphic region short allele). Clear-cut experimental support for genetic differential susceptibility emerged: the combined effect size of the interventions for the susceptible genotypes amounted to r =.33 (95% confidence interval = 0.23, 0.42; p