From the cultural genomics theoretical perspective, there is no one “best” genotype, as the best genotype varies as a function of the environment. A genotype that provides an advantage in one environment may be disadvantageous in another, with natural selection maintaining genetic variation when there is high variability in environments, as is the case for the human population today. Consistent with Differential Susceptibility Theory (Belsky & Pluess, 2009), individuals can vary in their sensitivity to socio-cultural conditions, including intervention, for reasons including their genotype. Consequently, understanding genetic influences on intervention response is critical. We tested an interaction between a polygenic environmental susceptibility score based on identical twin differences (Keers et al., 2016) and the Family Check-Up intervention, which focuses on improving positive parent management skills (Dishion & Stormshak, 2007).
Participants were a high risk, culturally diverse sample of children and their families drawn from the Early Steps Multisite randomized prevention trial and followed longitudinally (N=731; 13% Latino, 28% African American, 50% European American, 13% biracial, and 9% other groups). Families were randomly assigned (but gender balanced) to the control or intervention condition after the baseline assessment at child age 2 years. The polygenic susceptibility scores contained 2372 SNPs for a p=.05 threshold based on Keers and colleagues’ (2016) GWAS, and 4606 SNPs for p=.10. Covariates included age, gender, income, study site, and the first two of 20 ancestry principal components, examining main effects and two-way interactions (Keller, 2014). Symptoms of internalizing psychopathology were assessed through child report on the Diagnostic Interview Schedule for Children (DISC-IV) structured clinical interview conducted in the home when the children were 10 years of age.
As hypothesized, polygenic susceptibility moderated the effects of the intervention on children’s symptoms of internalizing psychopathology, such that children who were genetically susceptible to the socio-cultural environment and randomly assigned to the intervention group had fewer symptoms than children assigned to the control condition. A significant difference in self-reported DISC-IV internalizing symptoms emerged between the intervention and control groups for those 0.493 standard deviations above the mean on polygenic susceptibility, or approximately 25% of the sample.
With genetically informative designs, we can elucidate individual and socio-cultural differences in treatment response and individualize psychosocial interventions, reducing the burden of child psychopathology and maximizing wellbeing for children growing up in a wide range of physical environments and cultures.
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: differential susceptibility to environmental influences. Psychological Bulletin, 135(6), 885-908.
Dishion, T. J., & Stormshak, E. (2007). Intervening in children’s lives: An ecological, family-centered approach to mental health care. Washington, DC: American Psychological Association.
Keers, R., Coleman, J. R., Lester, K. J., Roberts, S., Breen, G., Thastum, M., ... & Nauta, M. (2016). A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders. Psychotherapy and Psychosomatics, 85, 146-158.
Keller, M. C. (2014). Gene× environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution. Biological Psychiatry, 75, 18-24.
Developmental Disorders (e.g. ADHD) , Evolution , Psychopathology (e.g., Internalizing, Externalizing, Psychosis) , Statistical Methods , Development
