Vasopressin and social behavior in humans: testing for genetic associations using a latent factor approach Open Access

Ficks, Courtney Alexandra (2014)

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Arginine vasopressin (AVP) is a neuropeptide that shows strong evolutionary conservation across species and has been demonstrated to play a role in a wide range of social behaviors. Several candidate gene studies have reported associations between the AVPR1a receptor gene, AVPR1A, and variation in social phenotypes in humans. Nonetheless, as studies of other candidate genes have also demonstrated, the magnitude and direction of effects for AVPR1A polymorphisms have been inconsistent and difficult to replicate, perhaps due to factors such as multiple testing and differences in linkage disequilibrium of SNPs between study samples. In the present dissertation we explored a method of testing for the effects of AVPR1A that allowed us to examine the effects of common variation across the gene using a single omnibus statistical test. Our sample included 621 children ages 6-18 years who were initially recruited from several sources. Children were genotyped for 8 single nucleotide polymorphisms (SNPs) in AVPR1A that were selected a priori to cover the majority (> 80%) of the variation across the gene. Parents provided reports of their children's behavior and temperament. Following a rigorous examination of genotyping quality, we tested for associations between AVPR1A and two social phenotypes (aggression and sociability) in analogous sets of structural equation models. In each model, the phenotype was modeled as a latent factor indicated by the parent-reported items for the scale of interest. Similarly, AVPR1A genotype was modeled as a separate latent factor indicated by the categorically-coded genotypes for each of the 8 SNPs. The latent phenotype factor was regressed on several covariates as well as the latent AVPR1A factor. Findings for these models demonstrated significant associations between AVPR1A and childhood aggression for both boys and girls. Associations were fairly robust to differences in sample size and the number of observations available per SNP. In contrast, AVPR1A was not associated with sociability. Overall, the proposed gene-based, latent factor approach to modeling genetic associations may facilitate more powerful and replicable tests of association for the effects of AVPR1A on social behavior than typical analytic methods practiced in candidate gene research.

Table of Contents

General Introduction 1 Paper 1: AVPR1A and aggression 24 Abstract 25 Introduction 27 Method 30 Results 39 Discussion 50 References 57 Tables 62 Paper 2: AVPR1A and prosocial behavior 79 Abstract 80 Introduction 81 Method 86 Results 90 Discussion 95 References 101 Tables 106 General Discussion 116 References 125 Appendices 139

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