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Cited by 279Neuroendocrine regulation and behaviorExperimental Behavioral Economics StudiesNeurotransmitter Receptor Influence on Behavior

The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task

Open access
Israel, Salomon, Lerer, Elad, Shalev, Idan, Uzefovsky, Florina, Riebold, Mathias, Laiba, Efrat, Bachner-Melman, Rachel, Maril, Anat +3 more·2009·PLoS ONE
DOI 10.1371/journal.pone.0005535PMC PMC2680041
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Abstract

BACKGROUND: Economic games observe social decision making in the laboratory that involves real money payoffs. 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). In the current investigation, the gene encoding the related oxytocin receptor (OXTR) was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO) task. METHODOLOGY/PRINCIPAL FINDINGS: Association (101 male and 102 female students) using a robust-family based test between 15 single tagging SNPs (htSNPs) across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001). Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2-5 locus haplotypes (p<0.05). A second sample of 98 female subjects was subsequently and independently recruited to play the dictator game and was genotyped for the three significant SNPs found in the first sample. The rs1042778 SNP was shown to be significant for the second sample as well (p = 0.004, Fisher's exact test). CONCLUSIONS: The demonstration that genetic polymorphisms for the OXTR are associated with human prosocial decision making converges with a large body of animal research showing that oxytocin is an important social hormone across vertebrates including Homo sapiens. Individual differences in prosocial behavior have been shown by twin studies to have a substantial genetic basis and the current investigation demonstrates that common variants in the oxytocin receptor gene, an important element of mammalian social circuitry, underlie such individual differences.

AI snapshot

Written from the paper’s full text.

TL;DR

Common variants in the oxytocin receptor gene (OXTR) were associated with prosocial fund allocations in both the Dictator Game and the Social Value Orientations task, with rs1042778 showing the most robust signal. The rs1042778 association with Dictator Game giving was replicated in an independent sample of 98 female subjects.

Key findings

  • In the first family-based sample (101 male and 102 female students), 8 of 15 analyzed OXTR htSNPs showed nominal association with one or both games; 6 of 8 were consistent across Dictator Game and SVO. The most significant SNP was rs1042778 for both Dictator Game (p = 0.001, corrected p = 0.016) and SVO (p = 0.002, corrected p = 0.031).
  • Three SNPs—rs1042778, rs2268490, and rs237887—were significant for both games. Haplotype analysis found significant associations for 2–5 locus haplotypes after permutation testing (p < 0.05); the 4-locus block rs9840864-rs237888-rs2268490-rs237887 was significant for Dictator Game (FBAT-GEE = 0.005), SVO (FBAT-GEE = 0.028), and jointly (p = 0.038).
  • Dictator Game and SVO allocations were correlated (Pearson Chi-Square = 28.18, DF = 1, p < 0.0001): 64.7% of SVO prosocial participants were high Dictator Game allocators versus 26.5% of proself participants.
  • In the second sample of 98 female subjects, rs1042778 was significant for high/low Dictator Game giving (p = 0.004, Fisher’s exact test); mean giving trended higher for GG+GT genotypes (25 shekels) than TT genotypes (18.3 shekels; F1,96 p = 0.07, effect size approximately 0.5 SD).

Methods

  • Candidate-gene family-based association study. First sample: 101 male and 102 female students, average age 26.00 (SD = 3.73), with parents genotyped for family-based analysis; second sample: 98 mothers, average age 34.47 (SD = 4.76), who played only the Dictator Game.
  • Sixteen tagging SNPs across OXTR were selected; rs2139184 was excluded for very low heterozygosity, leaving 15 htSNPs analyzed. Dictator Game allocations were dichotomized as low (<25 NIS) versus high (≥25 NIS); SVO responses were categorized as prosocial, proself, or undefined.
  • Main analyses used PBAT dominant model, UNPHASED haplotype analysis with 1000 permutations, and FBAT-GEE multivariate statistics; the second sample used Fisher’s exact test.

Limitations

  • The paper states that complex traits such as human altruism are shaped by environment and multiple genes and pose challenges from gene-gene and gene-environment interactions, genetic heterogeneity, low penetrance, and limited statistical power. It also notes that the second sample played only the Dictator Game because time constraints precluded the SVO, and that the pharmacological oxytocin study by Zak et al. did not find a Dictator Game effect, suggesting a future pharmacogenetic approach.
  • Evident from the text: the replication sample was all female mothers and tested only three SNPs, so replication is limited to Dictator Game giving and rs1042778 rather than the full OXTR region or SVO. The first sample also showed some sex-specific nominal associations, and many SNP results were nominal before correction.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0005535

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 36 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    6 of the 8 htSNPs showed a consistent association for both Dictator Game and SVO allocations.

    “6 of the 8 htSNPs showed a consistent association for both Dictator Game and SVO allocations.”
    Quote in the paperSubstantial claim
  • Findingown data

    Of the 15 htSNPs across the OXTR gene region, 8 showed nominal significant association with one or both of the game paradigms before correction for multiple testing.

    “Of the 15 htSNPs across the gene region, 8 htSNPs showed nominal significant association (before correction for multiple testing) with one or both of the game paradigms”
    Quote in the paperNot a substantial claim
  • Findingown data

    47% of participants were designated as high allocators in the Dictator Game.

    “Altogether, 47% of the participants were designated as high allocators.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Some SNPs showed gender-specific nominal associations, e.g. rs237897 in male subjects and rs9840864 in female subjects.

    “There were also SNPs whose effects appeared to be gender specific e.g. rs237897 (nominally significant in male subjects) and rs9840864 (nominally significant in female subjects).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Prosocial responses in the SVO task fell into a bi-modal distribution, with 38% of participants selecting 9/9 prosocial responses and 24% selecting 0/9.

    “Similar to dictator giving, prosocial responses also fell into a bi-modal distribution with a plurality (38%) of participants selecting 9/9 prosocial responses and 24% selecting 0/9.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 21
  • Classified as probably not a substantial claim. 38

  • May combine two claims.

    Findingown data

    In the SVO task, 58% of participants were categorized as prosocial, 36% as proself (1% competitive and 35% individualistic), and 6% as undefined.

    “58% of participants were categorized as prosocial, 36% as proself (which includes 1% competitive and 35% individualistic) and 6% as undefined.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A family-based analysis showed significant association of rs1042778 (p = 0.001), rs2268490 (p = 0.011), and rs237887 (p = 0.005) with prosocial value orientations.

    “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).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The PBAT association analysis assumes a dominant mode of inheritance.

  • May combine two claims.

    Findingown data

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

    “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).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the SVO prosocial group, 64.7% were also high allocators in the Dictator Game, whereas among proself SVO individuals only 26.5% were high allocators.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    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).

    “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).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    rs1042778 is significant in the prior autism study, in the first sample for both Dictator and SVO, and in the second independently recruited Dictator Game sample.

    “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.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [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 in the free run.

  • May combine two claims.

    Findingown data

    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 are jointly considered (p = 0.038).

    “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).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    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.

    “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).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In a prior study, intranasal oxytocin significantly increased transfer amounts in the Ultimatum game compared to placebo, whereas no effect in the Dictator Game was observed.

    “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”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] PJ Zak, 2007, Oxytocin increases generosity in humans., PLoS ONE source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    All SNPs tested were in Hardy-Weinberg Equilibrium (p > 0.01).

    “All of the SNPs tested were in Hardy-Weinberg Equilibrium (p>0.01).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The AVPR1a and oxytocin receptor (OXTR) genes contribute to autism spectrum disorders (ASD).

    “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.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [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 in the free run.

    • cites [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 in the free run.

    • cites [27]–[30]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Haplotypes are often more informative than individual SNPs.

    “Since haplotypes are often more informative than individual SNPs [36], haplotype analysis was carried out.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] DC Crawford, 2005, Definition And Clinical Importance Of Haplotypes., Annu Rev Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Selection of all tagging SNPs listed for OXTR in HapMap represents an optimal strategy for detecting association across this gene region.

    “Our selection of all tagging SNPs listed for OXTR in HapMap represents an optimal strategy for detecting association across this gene region [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] BV Halldorsson, 2004, Optimal selection of SNP markers for disease association studies., Hum Hered source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The classical economic assumption of self-interest cannot explain the richness of human social behavior.

    “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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] G Loewenstein, 2007, Neuroeconomics., Annu Rev Psychol

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    One tagging SNP, rs2139184, had a very low rate of heterozygosity and was excluded from the analysis.

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

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Intranasal application of oxytocin increases trusting behavior in humans.

    “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].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] T Baumgartner, 2008, Oxytocin shapes the neural circuitry of trust and trust adaptation in humans., Neuron source

      Not checked in the free run.

    • cites [21] M Kosfeld, 2005, Oxytocin increases trust in humans., Nature source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Arginine vasopressin (AVP) and oxytocin (OT) are key neuropeptides that facilitate social communication, affiliative behaviors and social cognition across mammals.

    “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] .”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [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 in the free run.

    • cites [7] LJ Young, 2004, The neurobiology of pair bonding., Nat Neurosci source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Fund allocation in the Dictator Game is considered a real-life test of altruism because giving is costly and not subject to strategic reciprocity, particularly when identities are anonymous.

    “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].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] CC Eckel, 1996, Altruism in Anonymous Dictator Games., Games and Economic Behavior source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Genetic association studies for complex phenotypes such as social behavior can be highly sensitive to measurement construct.

    “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].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] JA Schinka, 2004, A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety., Mol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Allocation of funds in the Dictator Game is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a).

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    93% of contacted individuals agreed to participate.

    “93% of contacted individuals agreed to participate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The FBAT statistic is robust against population admixture and stratification.

    “The FBAT statistic has an additional advantage in that it is robust against population admixture and stratification [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

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

    “The data analysis can be adjusted for covariates and gene/environment interactions.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source

      Not checked in the free run.

    • cites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Ordering of the Dictator Game and Social Value Orientations task was randomized.

    “Ordering of DG and SVO was randomized”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    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.

    “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.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source

      Not checked in the free run.

    • cites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

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

    “This methodology extends readily to scenarios in which the parental genotypes are not known, using the approach of Rabinowitz and Laird [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    UNPHASED is a suite of programs for association analysis of multilocus haplotypes from unphased genotype data.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] F Dudbridge, 2003, Pedigree disequilibrium tests for multilocus haplotypes., Genet Epidemiol source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The PBAT software package provides a unique set of tools for complex family-based association analysis at a genome-wide level.

    “The PBAT software package provides a unique set of tools for complex family-based association analysis at a genome-wide level [65], [66].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source

      Not checked in the free run.

    • cites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Twin studies underscore the importance of the genetic contribution to prosocial behavior.

    “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.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [58] A Knafo, 2006, Parental discipline and affection and children&apos;s prosocial behavior: genetic and environmental links., J Pers Soc Psychol source

      Not checked in the free run.

    • cites [59] A Knafo, 2006, Prosocial behavior from early to middle childhood: genetic and environmental influences on stability and change., Dev Psychol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

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

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

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    The permutation 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.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A specific motif of about 10-15 nucleotides close to the middle of the 3rd intron specifically binds nuclear proteins correlating with the down-regulated state of the OXTR gene.

    “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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

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

    “Haplotype-based features include sliding windows and the reconstruction of the haplotypes of the probands.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] KV Steen, 2005, PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies., Hum Genomics source

      Not checked in the free run.

    • cites [66] C Lange, 2004, PBAT: tools for family-based association studies., Am J Hum Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

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

    “Permutation test correction was performed using 1000 iterations (random permutations) and applied to correction of global P-values”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All subjects gave informed written consent.

    “All subjects gave informed written consent”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    To limit multiple testing, a more stringent criterion for SNP selection was used in the second sample, genotyping only the three SNPs found significant in both SVO and Dictator in the first sample (rs2268490, rs237887, rs1042778).

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] A Herbert, 2006, A common genetic variant is associated with adult and childhood obesity., Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Variations in the OXTR and AVPR1a genes jointly contribute to a complex human behavioral phenotype, probably as the rule rather than the exception.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The 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.

    “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.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Game instructions were identical for both groups.

    “Game instructions were identical for both groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

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

    “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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] AM Glazier, 2002, Finding genes that underlie complex traits., Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A number of 5′ upstream regulatory sites have been identified for the OXTR promoter region.

    “In addition, to this intronic regulation site, a number of 5′ upstream regulatory sites have been identified for the OXTR promoter region [57].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] AM Blanks, 2007, Regulation of oxytocin receptors and oxytocin receptor signaling., Semin Reprod Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The SVO measure was developed by Van Lange and colleagues using a series of decomposed games involving choices among combinations of outcomes for oneself and for another person.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] G Domes, 2007, Oxytocin attenuates amygdala responses to emotional faces regardless of valence., Biol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    3′ untranslated regions often contain several regulatory elements that govern the spatial and temporal expression of an mRNA.

    “3′ untranslated regions (3′ UTRs) often contain several regulatory elements that govern the spatial and temporal expression of an mRNA. [55]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] S Kuersten, 2003, The power of the 3′ UTR: translational control and development., Nat Rev Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    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.

    “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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] BV Halldorsson, 2004, Optimal selection of SNP markers for disease association studies., Hum Hered source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    There was no effect of game order on average giving amount or value orientation.

    “there was no effect of game order on average giving amount or value orientation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    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.

    “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.”
    Quote in the paperNot a substantial claim
48 of 48

  • The authors state this as an assumption.

    The PBAT association analysis assumes a dominant mode of inheritance.

    “results are given using PBAT's dominant model, which assumes a dominant mode of inheritance.”

  • The authors state this as an assumption.

    Under the null hypothesis, offspring genotypes follow Mendelian segregation.

    “which are assumed to follow Mendelian segregation under the null hypothesis.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The exercise of power increases testosterone and decreases oxytocin, which in turn leads to higher aggression and lower empathy and prosocial behaviour.

    “Furthermore, the exercise of power increases levels of testosterone while decreasing oxytocin which in turn leads to higher levels of aggression and lower levels of empathy and prosocial behaviour (Israel et al. 2009; Owen 2012; Hogeveen et al. 2014; Robertson 2012).”

    From Having Burned the Straw Man of Christian Spiritual Leadership, what can We Learn from Jesus About Leading Ethically? (2017) · cites this paper as Israel et al. 2009

    The Discussion (page unavailable) links variation in the oxytocin receptor gene to prosocial fund allocations, and the Introduction describes reported effects of oxytocin on social cognition. The paper does not establish that exercising power raises testosterone or lowers oxytocin, or that those changes cause greater aggression and reduced empathy and prosocial behaviour. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The social value orientation construct itself has been characterized by a specific haplotype of the OXTR gene.

    “The SVO construct itself has been characterized by a specific haplotype of the OXTR gene (Israel et al., 2009).”

    From The effect of oxytocin on cooperation in a prisoner's dilemma depends on the social context and a person's social value orientation (2014) · cites this paper as Israel et al., 2009

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Student sample sex counts are reversed

    Minor

    The abstract reports 101 male and 102 female students, while the Subjects section reports 102 men and 101 women for the same sample.

  • Primer table gives a different SNP identifier

    Minor

    The association results identify rs2268490 as one of the significant SNPs, but the corresponding identifier in the genotyping-primer table is rs2264890.

  • Table 1 supports seven, not eight, nominally significant SNPs

    Minor

    At p<0.05, Table 1 shows nominal significance for seven SNPs. The apparent eighth, rs13316193, has p = 0.0508, which is above that threshold.

3 of 3

Cites

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Cited by

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Related

Authors
Israel, S., Lerer, E., Shalev, I., Uzefovsky, F., Riebold, M., Laiba, E., Bachner-Melman, R., Maril, A., Bornstein, G., Knafo, A., & Ebstein, R. P.
Affiliations
Hebrew University of Jerusalem (IL)
Corresponding author
Ebstein, Richard P.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-05-20
Volume
4
Issue
5
Pages
e5535
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0005535
PMC
PMC2680041
OpenAlex
W2039329578
Semantic Scholar
275c7845659b70b3d7a9b0af2c118a646b9ec7a3
Cited by
278
References
68
Citations by year
2026: 2 · 2025: 1 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 16 · 2020: 17 · 2019: 9 · 2018: 15 · 2017: 13 · 2016: 22 · 2015: 20 · 2014: 26 · 2013: 32 · 2012: 30
FWCI
35.25
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Hebrew University of Jerusalem
  • Israel Academy of Sciences and Humanities
  • Israel Science Foundation
  • Ministry of Industry, Trade and Labor
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Social Sciences › Safety Research › Experimental Behavioral Economics Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
oxytocin receptor, dictator game, prosocial behavior, altruism, genetic association, single nucleotide polymorphisms, haplotypes, individual differences, social decision-making, oxytocin
MeSH terms
Adult, Cost Allocation, Female, Games, Experimental, Haplotypes, Humans, Male, Social Behavior, Social Values, Software, Task Performance and Analysis, Receptors, Oxytocin, Polymorphism, Single Nucleotide

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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