The Oxytocin Receptor (OXTR) Contributes to Prosocial Fund Allocations in the Dictator Game and the Social Value Orientations Task

In the paper

“58% of participants were categorized as prosocial, 36% as proself (which includes 1% competitive and 35% individualistic) and 6% as undefined.”

In the paper

“For Dictator Giving, significant associations were observed for 2–8 locus haplotypes (global p<0.05), many of which were also significant for the SVO.”

In the paper

“A family-based analysis for the three SNPs showed significant association with prosocial value orientations (PBAT dominant model: rs1042778 p = 0.001, rs2268490 p = 0.011, and rs237887 p = 0.005).”

In the paper

“The most significant association, which is also robust to Bonferroni correction, was observed with rs1042778 for both the Dictator Game (p = 0.001, p corrected 0.016) and SVO (p = 0.002, p corrected = 0.031).”

In the paper

“In the SVO prosocial group, 64.7% of respondents are also high allocators (≥25 NIS) in the Dictator Game. Among proself SVO individuals, only 26.5% are high allocators in the Dictator Game.”

In the paper

“Following permutation testing, significance was observed for 2–5 locus haplotypes (p<0.05) and approached significance for the 7 and 8 locus haplotypes (permutation test p<0.1).”

In the paper

“Of particular interest is rs1042778, which is significant both in our prior autism study[25], the 1st sample for both Dictator and SVO and in the second independently recruited DG sample.”

What the sources say

• Not checked yetcites [25] E Lerer, 2008, Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition., Mol Psychiatry source

In the paper

“Notably, the 4 locus haplotype block (rs9840864-rs237888-rs2268490-rs237887) is significant for Dictator Giving (FBAT-GEE = 0.005), SVO (FBAT-GEE = 0.028) and when both Dictator Giving and SVO are jointly considered (p = 0.038).”

In the paper

“Dictator giving was considerably higher in the second sample (One-way ANOVA F1,296 = 9.934 p = 0.002), with giving amounts on average 4.97 higher in the second sample (see Figure 1).”

In the paper

“A recent study by Zak et al.,[31] had subjects indicate transfer amounts for both the DG and the Ultimatum game (where the recipient has the opportunity to refuse the allocation, in which case both players receive zero) after undergoing intranasal administration of OT. Oxytocin significantly increased transfer amounts in the Ultimatum game as compared to placebo, whereas no effect in the DG was ob”

What the sources say

• Not checked yetcites [31] PJ Zak, 2007, Oxytocin increases generosity in humans., PLoS ONE source

In the paper

“All of the SNPs tested were in Hardy-Weinberg Equilibrium (p>0.01).”

In the paper

“In addition to their roles in enhancing social behaviors, the AVPR1a and oxytocin receptor (OXTR) genes have been shown by us [25], [26] and others [27]–[30] to contribute to autism spectrum disorders (ASD), a behavioral disorder characterized by deficits in social communication and bonding.”

What the sources say

• Not checked yetcites [25] E Lerer, 2008, Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition., Mol Psychiatry source
• Not checked yetcites [26] N Yirmiya, 2006, Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills., Mol Psychiatry source
• Not checked yetcites [27]–[30]

In the paper

“Since haplotypes are often more informative than individual SNPs [36], haplotype analysis was carried out.”

What the sources say

• Not checked yetcites [36] DC Crawford, 2005, Definition And Clinical Importance Of Haplotypes., Annu Rev Med source

In the paper

“Our selection of all tagging SNPs listed for OXTR in HapMap represents an optimal strategy for detecting association across this gene region [35].”

What the sources say

• Not checked yetcites [35] BV Halldorsson, 2004, Optimal selection of SNP markers for disease association studies., Hum Hered source

In the paper

“An important contribution of neuroeconomics is the demonstration that the classical economic assumption of self-interest cannot explain the richness of human social behavior [1].”

What the sources say

• Not checked yetcites [1] G Loewenstein, 2007, Neuroeconomics., Annu Rev Psychol

In the paper

“Of the 16 tagging SNPs, one of them, rs2139184, had a very low rate of heterozygosity, and was not included in the analysis.”

In the paper

“Intriguingly, intranasal application of OT has been shown to increase trusting behavior in humans [20], [21], identification of others' affective states [22] and amygdala responses to emotional faces [23].”

What the sources say

• Not checked yetcites [20] T Baumgartner, 2008, Oxytocin shapes the neural circuitry of trust and trust adaptation in humans., Neuron source
• Not checked yetcites [21] M Kosfeld, 2005, Oxytocin increases trust in humans., Nature source

In the paper

“Our first studies of the role of the AVPR1a gene in social cognition exemplified by a simple laboratory paradigm converges with a wide range of both animal and human experimentation showing that arginine vasopressin (AVP) and the closely related oxytocin (OT) are key neuropeptides that facilitate social communication, affiliative behaviors and social cognition across mammals [6], [7] .”

What the sources say

• Not checked yetcites [6] AJ Bartz, 2006, The neuroscience of affiliation: Forging links between basic and clinical research on neuropeptides and social behavior., Horm Behav source
• Not checked yetcites [7] LJ Young, 2004, The neurobiology of pair bonding., Nat Neurosci source

In the paper

“Fund allocation in the Dictator Game is considered a real-life test of altruism since it involves a ‘put your money where your mouth is’ decision where giving to another is both costly and not subject to strategic considerations of reciprocity; this is particularly the case when “Dictator” and “Recipient” identities are made anonymous [4].”

What the sources say

• Not checked yetcites [4] CC Eckel, 1996, Altruism in Anonymous Dictator Games., Games and Economic Behavior source

In the paper

“Genetic association studies for complex phenotypes such as social behavior can be highly sensitive to measurement construct. For example, a meta-analysis reviewing association for a serotonin transporter gene polymorphism (5-HTTLPR) and anxiety related traits demonstrated how choice of measurement scale may be a critical factor in moderating phenotypic contours[32].”

What the sources say

• Not checked yetcites [32] JA Schinka, 2004, A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety., Mol Psychiatry source

In the paper

“Previously we have shown that allocation of funds in the Dictator Game (DG), a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a).”

• Also stated in: § Introduction · boosted

  “In a seminal study [3] we have shown that the powerful techniques of molecular genetics can also be employed to further clarify the mechanisms by which the social brain formulates economic decisions. We demonstrated that allocation of funds in the Dictator Game (DG) were in part determined by length of the arginine vasopressin 1a (AVPR1a) RS3 promoter region repeat region.”

What the sources say

• Not checked yetcites [3] A Knafo, 2007, Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA., Genes Brain Behav

In the paper

“93% of contacted individuals agreed to participate.”

In the paper

“The FBAT statistic has an additional advantage in that it is robust against population admixture and stratification [67].”

What the sources say

• Not checked yetcites [67] D Rabinowitz, 2000, A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information., Hum Hered source

In the paper

“The data analysis can be adjusted for covariates and gene/environment interactions.”

What the sources say

• Not checked yetcites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source
• Not checked yetcites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

In the paper

“Ordering of DG and SVO was randomized”

In the paper

“PBAT can handle nuclear families with missing parental genotypes, extended pedigrees with missing genotypic information, analysis of single nucleotide polymorphisms (SNPs), haplotype analysis, quantitative traits, multivariate/longitudinal data and time to onset phenotypes.”

What the sources say

• Not checked yetcites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source
• Not checked yetcites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

In the paper

“This methodology extends readily to scenarios in which the parental genotypes are not known, using the approach of Rabinowitz and Laird [67].”

What the sources say

• Not checked yetcites [67] D Rabinowitz, 2000, A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information., Hum Hered source

In the paper

“The various tests we used are implemented in the program UNPHASED (http://www.rfcgr.mrc.ac.uk/~fdudbrid/software/unphased/) [63], a suite of programs for association analysis of multilocus haplotypes from unphased genotype data.”

What the sources say

• Not checked yetcites [63] F Dudbridge, 2003, Pedigree disequilibrium tests for multilocus haplotypes., Genet Epidemiol source

In the paper

“The PBAT software package provides a unique set of tools for complex family-based association analysis at a genome-wide level [65], [66].”

What the sources say

• Not checked yetcites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source
• Not checked yetcites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

In the paper

“Although twin studies underscore the importance of the genetic contribution to prosocial behavior [58], [59], untangling the contribution of specific polymorphisms to this and other complex traits is difficult.”

What the sources say

• Not checked yetcites [58] A Knafo, 2006, Parental discipline and affection and children's prosocial behavior: genetic and environmental links., J Pers Soc Psychol source
• Not checked yetcites [59] A Knafo, 2006, Prosocial behavior from early to middle childhood: genetic and environmental influences on stability and change., Dev Psychol source

In the paper

“SNP marker selection is aimed to increase the chances that at least one typed SNP would be in linkage disequilibrium (LD) with the disease causative variant, while at the same time controlling the cost of the study in terms of the number of markers genotyped and sampled.”

In the paper

“the genetic study was approved by the local University and Hospital Internal Review Board and the Israeli Ministry of Health (Genetics Section).”

In the paper

“This procedure corrects for multiple testing but accounts for correlation between markers, hence is less conservative than a Bonferroni correction, which is appropriate for independent tests such as unlinked markers.”

In the paper

“Suggestion of a functional character of SNPs located in the 3rd intron is based on the finding of a specific motif of about 10–15 nucleotides close to the middle of the 3rd intron that specifically binds nuclear proteins correlating with the down-regulated state of the gene [56].”

What the sources say

• Not checked yetcites [56] Y Mizumoto, 1997, A genomic element within the third intron of the human oxytocin receptor gene may be involved in transcriptional suppression., Mol Cell Endocrinol source

In the paper

“Haplotype-based features include sliding windows and the reconstruction of the haplotypes of the probands.”

What the sources say

• Not checked yetcites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source
• Not checked yetcites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

In the paper

“Permutation test correction was performed using 1000 iterations (random permutations) and applied to correction of global P-values”

In the paper

“All subjects gave informed written consent”

In the paper

“To limit the conundrum of multiple testing, we used a more stringent criteria for SNP selection in the second sample[39]. Subjects were genotyped solely for the three SNPs found to be significant in both the SVO and Dictator in the first sample (rs2268490, rs237887 and rs1042778).”

What the sources say

• Not checked yetcites [39] A Herbert, 2006, A common genetic variant is associated with adult and childhood obesity., Science source

In the paper

“That variations in these two receptor genes, OXTR and AVPR1a, jointly contribute to a complex human behavioral phenotype is probably the rule and not the exception.”

In the paper

“Additionally, our finding of a significant association for both the Dictator game and SVO, decision tasks that are significantly correlated with one another, provides supporting evidence for the robustness of the current findings.”

In the paper

“Game instructions were identical for both groups.”

In the paper

“Complex traits including human altruism are molded by both environment and multiple genes and such phenotypes pose special challenges for genetic analysis due to gene-gene and gene-environment interactions, genetic heterogeneity, low penetrance, and limited statistical power [60].”

What the sources say

• Not checked yetcites [60] AM Glazier, 2002, Finding genes that underlie complex traits., Science source

In the paper

“In addition, to this intronic regulation site, a number of 5′ upstream regulatory sites have been identified for the OXTR promoter region [57].”

What the sources say

• Not checked yetcites [57] AM Blanks, 2007, Regulation of oxytocin receptors and oxytocin receptor signaling., Semin Reprod Med source

In the paper

“A measure developed by Van Lange and colleagues (23) to measure social value orientations by using a series of decomposed games, involving choices among combinations of outcomes for oneself and for another person, was adapted in this study.”

What the sources say

• Not checked yetcites [23] G Domes, 2007, Oxytocin attenuates amygdala responses to emotional faces regardless of valence., Biol Psychiatry source

In the paper

“3′ untranslated regions (3′ UTRs) often contain several regulatory elements that govern the spatial and temporal expression of an mRNA. [55]”

What the sources say

• Not checked yetcites [55] S Kuersten, 2003, The power of the 3′ UTR: translational control and development., Nat Rev Genet source

In the paper

“Most association studies rely on the use of surrogate markers, single-nucleotide polymorphisms (SNPs) being the most suitable due to their abundance and ease of scoring (see discussion in [35].”

What the sources say

• Not checked yetcites [35] BV Halldorsson, 2004, Optimal selection of SNP markers for disease association studies., Hum Hered source

In the paper

“there was no effect of game order on average giving amount or value orientation.”

In the paper

“Empirical studies reporting block-like segments in the genome with high LD and low haplotype diversity have motivated a marker selection strategy whereby subsets of SNPs that ‘tag’ the common haplotypes of a region are picked for genotyping, avoiding typing redundant SNPs.”