Association of the Oxytocin Receptor Gene (OXTR) with Childhood Aggression and Social Cognition Open Access

Poore, Holly Elizabeth (2017)

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Aggression is a complex trait, influenced by a multitude of factors and has important implications for long-term life outcomes. Behavior genetic studies have found that aggression is moderately to highly heritable across the lifespan. Despite its high heritability, molecular genetic studies of aggression have had mixed results, with few genetic variants showing reliable associations. Recent research suggests that Oxytocin and the Oxytocin Receptor Gene (OXTR) influences social cognition and behavior in humans and animal models. The primary aim of this study is to examine associations between OXTR and measures of aggression in children and adolescents. Based on current animal models, it is hypothesized that OXTR will be associated with various forms of aggression. In the current investigation, we collected DNA and parent ratings of aggression for a total of 636 children ages 6-18 years old sampled from both unreferred twins as well as clinically-referred children. The investigation included 31 SNPs in OXTR. To operationalize OXTR in a gene-based test, a series of Exploratory Structural Equation Models (ESEMs) of the OXTR SNPs were conducted. The model with five factors fit best while still favoring parsimony and was used to characterize the underlying structure of the gene. Aggression was also modeled as both a unitary aggression factor and as two separate reactive and proactive aggression factors. A series of gene-based tests were then conducted such that the aggression factors were regressed on the latent OXTR factors and all covariates. The OXTR factors accounted for a significant portion of the variance in the unitary aggression factor (R2 = 1.8%, p<.001), reactive aggression (R2 = 1.2%, p<.001), and proactive aggression (R2 = 5.8%, p<.001) over and above the contribution of the covariates. Social cognitive variables were available for a subsample of participants and the association between OXTR and social cognition was also examined. One through four factor models of OXTR were used in the association analyses between OXTR and social cognition. OXTR consistently accounted for a significant proportion of variance in the percentage of correct responses in the sad and fearful emotion categories and the number of commission errors in the happy and angry emotion categories across the two, three, and four factor models of OXTR. Future research will focus on replicating these results in larger samples from a diverse group of cohorts.

Table of Contents

Table of Contents

Introduction 1

Method 12

Data Analysis 14

Results 20

General Discussion 29

Implications for Gene Based Tests using Structural Equation Modeling 33

Limitations/Future Directions 34

References 37

Tables 45

Figures 57

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