Genetic polymorphisms in the serotonin, dopamine and opioid pathways influence social attention in rhesus macaques (Macaca mulatta)

Abstract

Behaviour has a significant heritable component; however, unpicking the variants of interest in the neural circuits and molecular pathways that underpin these has proven difficult. Here, we present a comprehensive analysis of the relationship between known and new candidate genes from identified pathways and key behaviours for survival in 109 adult rhesus macaques (Macaca mulatta). Eight genes involved in emotion were analysed for variation at a total of nine loci. Genetic data were then correlated with cognitive and observational measures of behaviour associated with wellbeing and survival using MCMC-based Bayesian GLMM in R, to account for relatedness within the macaque population. For four loci the variants genotyped were length polymorphisms (SLC6A4 5-hydroxytryptamine transporter length-polymorphic repeat (5-HTTLPR), SLC6A4 STin polymorphism, Tryptophan 5-hydroxylase 2 (TPH2) and Monoamine oxidase A (MAOA)) whilst for the other five (5-hydroxytryptamine receptor 2A (HTR2A), Dopamine Receptor D4 (DRD4), Oxytocin receptor (OXTR), Arginine vasopressin receptor 1A (AVPR1a), Opioid receptor mu(μ) 1 (OPRM1)) SNPs were analysed. STin genotype, DRD4 haplotype and OXTR haplotype were significantly associated with the cognitive and observational measures of behaviour associated with wellbeing and survival. Genotype for 5-HTTLPR, STin and AVPR1a, and haplotype for HTR2A, DRD4 and OXTR were significantly associated with the duration of behaviours including fear and anxiety. Understanding the biological underpinnings of individual variation in negative emotion (e.g., fear and anxiety), together with their impact on social behaviour (e.g., social attention including vigilance for threat) has application for managing primate populations in the wild and captivity, as well as potential translational application for understanding of the genetic basis of emotions in humans.