Heritability of social behavioral phenotypes and preliminary associations with autism spectrum disorder risk genes in rhesus macaques: A whole exome sequencing study

Abstract

Nonhuman primates and especially rhesus macaques (Macaca mulatta) have been indispensable animal models for studies of various aspects of neurobiology, developmental psychology, and other aspects of neuroscience. While remarkable progress has been made in our understanding of influences on atypical human social behavior, such as that observed in autism spectrum disorders (ASD), many significant questions remain. Improved understanding of the relationships among variation in specific genes and variation in expressed social behavior in a nonhuman primate would benefit efforts to investigate risk factors, developmental mechanisms, and potential therapies for behavioral disorders including ASD. To study genetic influences on key aspects of social behavior and interactions—individual competence and/or motivation for specific aspects of social behavior—we quantified individual variation in social interactions among juvenile rhesus macaques using both a standard macaque ethogram and a macaque‐relevant modification of the human Social Responsiveness Scale. Our analyses demonstrate that various aspects of juvenile social behavior exhibit significant genetic heritability, with estimated quantitative genetic effects similar to that described for ASD in human children. We also performed exome sequencing and analyzed variants in 143 genes previously suggested to influence risk for human ASD. We find preliminary evidence for genetic association between specific variants and both individual behaviors and multi‐behavioral factor scores. To our knowledge, this is the first demonstration that spontaneous social behaviors performed by free‐ranging juvenile rhesus macaques display significant genetic heritability and then to use exome sequencing data to examine potential macaque genetic associations in genes associated with human ASD.

Sensing Echoes: Temporal Misalignment in Auditory Brainstem Responses as the Earliest Marker of Neurodevelopmental Derailment

“…Recent biological evidence supports the notion that at least some forms (and probably the majority) of the broad, heterogeneous developmental disorders within the autism spectrum (ASD) are atypical prior to birth, many linked to genetic origins (11)(12)(13). These in turn, may have significant effects on postnatal development (14)(15)(16)(17).…”

Environmental, sex-specific and genetic determinants of infant social behaviour in a wild primate

“…In humans and non-human vertebrates, variation in affiliative social behaviour tends to be weakly, but measurably, heritable (e.g. in comparison to morphological or life-history traits [37][38][39][40][41][42][43][44][45][46][47]). However, in the absence of studies of the heritability of behavioural development in wild populations, the relative contributions of genes versus the environment, and the degree to which developmental features of social behaviour can respond to natural selection, remain unknown.…”

Rhesus monkey sociality is stable across time and linked to variation in the initiation but not receipt of prosocial behavior

“…We and others have been studying naturally occurring variation in primate sociality for a number of years, employing multiple and diverse methodologies, with a focus on rhesus monkeys. These efforts have included use of instantaneous and scan sampling (to study the type and frequency of social and nonsocial behaviors) (Gunter et al, 2022; Kovacs‐Balint et al, 2021; Parker et al, 2018), a personality rating instrument (to study variation in a personality dimension called Sociability) (Capitanio, 1999; Stevenson‐Hinde et al, 1980), and a macaque‐adapted version of a human instrument, the Social Responsiveness Scale (to study quantitative variation in social and autistic‐like traits) (Constantino & Gruber, 2005, 2012; Feczko et al, 2016; Kovacs‐Balint et al, 2021; Talbot et al, 2020, 2021). A consistent picture has now emerged showing that low‐social monkeys initiate fewer affiliative interactions (Capitanio, 1999), spend less time in contact and grooming with conspecifics (Capitanio, 1999; Parker et al, 2018), and demonstrate deficiency in species‐typical social information processing (including face recognition and gaze aversion) compared to high‐social monkeys (Capitanio, 2002; Sclafani et al, 2016).…”