Author:

Keywords:

gene-by-environment interactions, externalizing behavior, adolescents, parenting

Abstract:

Introduction. The current presentation reports on two approaches to study gene-by-environment (GxE) interactions predicting externalizing behavior in adolescents, with parenting as the environmental factor. In both approaches, we examine three alternative G×E hypotheses: diathesis stress, vantage sensitivity, and differential susceptibility (Pluess & Belsky, 2013). First, we examine within the frequently adopted single candidate gene approach whether adolescents exposed to specific ways of parenting differ in externalizing behavior, depending on variants of the dopamine transporter (DAT1) or dopamine receptor D4 (DRD4) genes. Externalizing problem behavior has been associated with dopaminergic neurotransmission in the human brain given its involvement in reward-based learning and motivation (Matthys, Vanderschuren, & Schutter, 2013). However, current criticism on single gene analyses is that they are unlikely to reveal practically important main effects and G×E interactions, because genes function and interact within biological pathways or networks (Ramanan, Shen, Moore, & Saykin, 2012). Therefore, we perform pathway analysis as a second approach to examine the same research questions. Based on an extensive literature survey, we created a genetic pathway by aggregating single nucleotide polymorphisms (SNPs) that were found to be significant predictors of externalizing behavior in genome-wide association (GWA) studies. Methods. Analyses are ongoing and are performed on a large sample of approximately 1000 seventh till ninth grade adolescents (51% boys; Mage = 13.79, SD = .93) of the first wave of the STRATEGIES project (Studying Transactions in Adolescence: Testing Genes in Interaction with Environments). Adolescents donated saliva samples to extract genetic information. Further, adolescents, their mothers and fathers completed questionnaires on (a) parenting behavior: support and four types of control (i.e., proactive, punitive, harsh punitive and psychological control; Janssens et al., 2014), and (b) adolescent externalizing problem behavior (Child Behavior Checklist, Youth Self Report). Results. Results of the single candidate genes analyses showed support for differential susceptibility in adolescents with the long DRD4 allele (no significant effects were found with the DAT1). They proved to be more susceptible to both low and high levels of proactive control by parents with regard to externalizing, and more specifically aggressive behavior. For adolescents with the long DRD4 variant, more proactive control was related to less problem behavior, whereas lower levels of proactive control were associated with more externalizing behavior. We also found a main effect of the DRD4 gene (i.e., less externalizing and aggressive behavior in long carriers) and main effects of parenting behavior (i.e., less externalizing problems were associated with support and proactive control, but more problems with punitive, harsh punitive, and psychological control). Most results were consistent across parent and adolescent ratings. We are currently conducting analyses in which we apply the genetic pathway approach. Discussion. The results of the two methods in G×E research will be compared and critically evaluated. Considering these two approaches simultaneously with regard to the same research questions might provide important insights and guidelines for future research.