Weak effects of common genetic variation in oxytocin and vasopressin receptor genes on rhesus macaque social behavior

Madlon-Kay, Seth; Montague, Michael J.; Brent, Lauren J. N.; Ellis, Stephen; Zhong, Brian L.; Snyder‐Mackler, Noah; Horvath, Julie E.; Skene, J. H. Pate; Platt, Michael L.

doi:10.1002/ajp.22873

Cited by 19 publications

(11 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are consistent with [18], who also investigated rhOXTR markers and social behavior in a similarly-sized sample of rhesus and likewise found no significant effects. We agree with their conclusions that behavioral genetic studies in NHPs likely face the same challenges as in humans: First, samples upwards of tens of thousands would be required to be adequately powered.…”

Section: Discussionsupporting

confidence: 92%

Heritability and relationship of oxytocin receptor gene variants with social behavior and central oxytocin in colony-reared adult female rhesus macaques

Leon

Walum²,

McCormack

et al. 2019

Preprint

View full text Add to dashboard Cite

The genetic contributions to sociality are an important research focus for understanding individual variation in social function and risk of social deficits in neurodevelopmental disorders (e.g. autism). The neuropeptide oxytocin (OXT) and its receptor, OXTR, influence social behavior across species. In humans and animals, common variants within the OXTR gene (OXTR) have been associated with varying socio-behavioral traits. However, the reported magnitude of influence of individual variants on complex behavior has been inconsistent. Compared to human studies, non-human primate (NHP) studies in controlled environments have the potential to result in robust effects detectable in relatively small samples. Here we estimate heritability of social behavior and central OXT concentrations in 214 socially-housed adult female rhesus macaques, a species sharing high similarity with humans in genetics, physiology, brain and social complexity. We present a bioinformatically-informed approach for identifying single nucleotide polymorphisms (SNPs) with likely biological relevance. We tested 13 common SNPs in regulatory and coding regions of OXTR for associations with behavior (pro-social, anxiety-like, and aggressive) and OXT concentration in cerebrospinal fluid (CSF). We found moderate rates of heritability for both social behavior and CSF OXT concentrations. No tested SNPs showed significant associations with behaviors or CSF in this sample. Associations between OXT CSF and social behavior were not significant either. SNP effect sizes were generally comparable to those reported in human studies of complex traits. While environmental control and a socio-biological similarity with humans is an advantage of rhesus models for detecting smaller genetic effects, it is insufficient to obviate large sample sizes necessary for appropriate statistical power.

show abstract

Section: Discussionsupporting

confidence: 92%

Heritability and relationship of oxytocin receptor gene variants with social behavior and central oxytocin in colony-reared adult female rhesus macaques

Leon

Walum²,

McCormack

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Also, studies on captive NHPs provide a more restricted and controlled environment (e.g., controlled diet, less habitat variation), which might lead to stronger genetic effects. A recent study on the effects of variants in OXTR and AVP receptor genes (AVPR1A, AVPR1B) on behavior in rhesus macaques, however, failed to replicate previous results and showed only very small effects of the 12 SNPs that were examined (Madlon-Kay et al 2018). Alongside the emerging consistency of findings that single genetic variants have only small effects on complex traits, Madlon-Kay and colleagues (2018) discuss other methodological difficulties, including missing control of genetic relatedness within the population and/or missing adjustment of pvalues, that raise doubt about earlier positive results.…”

Section: Gene-environment Interplaymentioning

confidence: 75%

Developing individual differences in primate behavior: the role of genes, environment, and their interplay

Borell

Weiss

Penke

2019

Behav Ecol Sociobiol

View full text Add to dashboard Cite

As is the case for humans, it has long been thought that nonhuman primates can be described in terms of their personality. Scientific observations that support this view include the presence of individual differences in social behavior and that they are relatively stable throughout life. Consequently, individuals are constrained in their behavioral flexibility when dealing with various environmental challenges. Still, the variation among individuals during development suggests that the environment influences how primates behave. Research in fields including psychology, behavior genetics, and behavioral ecology have tried to identify the mechanisms responsible for this interplay of behavioral stability and change. In this review we integrate theories and findings from research on humans and nonhuman primates that highlight how and to what extent genetic and environmental contributions shape the development of social behavior. To do so we first provide an overview and define what is meant by mean level and rank-order change of behavior. We then review explanations of behavioral stability and change, focusing on the role of genetic effects, how environmental circumstances influence behavioral variation throughout development, and how genetic and environmental influences may interact to produce this variation. Finally, we point to future research directions that could help us to further understand the development of social behavior in primates from within a behavior genetics framework.

show abstract

“…Links between vasopressin and other aspects of social behavior, on the other hand, have been demonstrated in both apes and monkeys. In rhesus macaques, variation in sociability is associated with measures of vasopressin in cerebral spinal fluid, despite no significant associations between AVPR1A alleles and social behaviors, such as grooming, passive contact, approaches and aggression . In chimpanzees, several studies have shown that polymorphisms in AVPR1A are associated with individual variation in different dimensions of personality, including social “smarts” (using coalitions and engaging in reciprocal grooming and play) and sociability .…”

Section: Introductionmentioning

confidence: 99%

AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees

Mulholland

Navabpour

Mareno

et al. 2020

Genes Brain and Behavior

View full text Add to dashboard Cite

The vasopressin system has been implicated in the regulation of social behavior and cognition in humans, nonhuman primates and other social mammals. In chimpanzees, polymorphisms in the vasopressin V1a receptor gene (AVPR1A) have been associated with social dimensions of personality, as well as to responses to sociocommunicative cues and mirror self‐recognition. Despite evidence of this association with social cognition and behavior, there is little research on the neuroanatomical correlates of AVPR1A variation. In the current study, we tested the association between AVPR1A polymorphisms in the RS3 promotor region and gray matter covariation in chimpanzees using magnetic resonance imaging and source‐based morphometry. The analysis identified 13 independent brain components, three of which differed significantly in covariation between the two AVPR1A genotypes (DupB−/− and DupB+/−; P < .05). DupB+/− chimpanzees showed greater covariation in gray matter in the premotor and prefrontal cortex, basal forebrain, lunate and cingulate cortex, and lesser gray matter covariation in the superior temporal sulcus and postcentral sulcus. Some of these regions were previously found to differ in vasopressin and oxytocin neural fibers between nonhuman primates, and in AVPR1A gene expression in humans with different RS3 alleles. This is the first report of an association between AVPR1A and gray matter covariation in nonhuman primates, and specifically links an AVPR1A polymorphism to structural variation in the social brain network. These results further affirm the value of chimpanzees as a model species for investigating the relationship between genetic variation, brain structure and social cognition with relevance to psychiatric disorders, including autism.

show abstract

Weak effects of common genetic variation in oxytocin and vasopressin receptor genes on rhesus macaque social behavior

Cited by 19 publications

References 92 publications

Heritability and relationship of oxytocin receptor gene variants with social behavior and central oxytocin in colony-reared adult female rhesus macaques

Heritability and relationship of oxytocin receptor gene variants with social behavior and central oxytocin in colony-reared adult female rhesus macaques

Developing individual differences in primate behavior: the role of genes, environment, and their interplay

AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees

Contact Info

Product

Resources

About