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Cited by 207Neuroendocrine regulation and behaviorNeurotransmitter Receptor Influence on BehaviorExperimental Behavioral Economics Studies

Oxytocin receptor genetic variation promotes human trust behavior

Open access
Krueger, Frank, Parasuraman, Raja, Iyengar, Vijeth, Thornburg, Matthew, Weel, Jaap, Lin, Mingkuan, Clarke, Ellen, McCabe, Kevin +1 more·2012·Frontiers in Human Neuroscience
DOI 10.3389/fnhum.2012.00004PMC PMC3270329
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Abstract

Given that human trust behavior is heritable and intranasal administration of oxytocin enhances trust, the oxytocin receptor (OXTR) gene is an excellent candidate to investigate genetic contributions to individual variations in trust behavior. Although a single-nucleotide polymorphism involving an adenine (A)/guanine (G) transition (rs53576) has been associated with socio-emotional phenotypes, its link to trust behavior is unclear. We combined genotyping of healthy male students (n = 108) with the administration of a trust game experiment. Our results show that a common occurring genetic variation (rs53576) in the OXTR gene is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors. Individuals homozygous for the G allele (GG) showed higher trust behavior than individuals with A allele carriers (AA/AG). Although the molecular functionality of this polymorphism is still unknown, future research should clarify how the OXTR gene interacts with other genes and the environment in promoting socio-emotional behaviors.

AI snapshot

Written from the paper’s full text.

TL;DR

In 108 healthy male students, the OXTR rs53576 G allele was associated with higher trust behavior in a laboratory trust game, but not with trustworthiness or risk behavior. The authors conclude that OXTR rs53576 may contribute specifically to observer-dependent trust during social interaction, while calling for cautious replication.

Key findings

  • Participants homozygous for the G allele (GG; n = 56) transferred 14% more money than A allele carriers (AG/AA; n = 52) at the maximal trust level [χ² = 11.9, P < 0.0001, corrected P < 0.001, Cohen’s d = 0.7].
  • The AG and AA groups did not differ at the maximal trust level (AG: 0.41 ± 0.04, AA: 0.44 ± 0.05; χ² = 0.2, P = 0.706).
  • No significant genotype group effects were found for investor transfers in the risk experiment or for trustee back transfers in the trust experiment.
  • Psychological controls largely did not differ by genotype, except the GG group had higher dispositional empathy [IRI: 2.7 ± 0.1 vs. 2.5 ± 0.1; t(106) = 1.8, P = 0.039, one-sided, Cohen’s d = 2.0], but empathy was not associated with trust, risk, or trustworthy behavior (rs < 0.11, Ps > 0.512).

Methods

  • Candidate gene study genotyping OXTR rs53576 in 108 healthy right-handed male students of European ancestry (mean age 20.2 ± 2.2 years), combined with a laboratory trust game and a lottery risk game.
  • In the trust game, investors could send 0–10 monetary units to a trustee; the amount was tripled, and trustees decided how much to return. Participants made five decisions each as investor and trustee with different randomly selected partners; the risk game used the same payoff structure without a social partner.
  • Genotype distribution was GG = 56, AG = 43, AA = 9 and met Hardy-Weinberg equilibrium [χ²(1) = 0.03, P = 0.854]. Analyses used mixed ANOVAs, follow-up Pearson chi-square tests with Bonferroni correction, Cohen’s d, and independent-samples t-tests for control measures.

Limitations

  • Stated: the sample size was modest, so findings could reflect the “winner’s curse” and overestimated effect sizes; the authors also note that the molecular functionality of rs53576 is unknown and the observed effect may reflect variants in linkage disequilibrium with rs53576.
  • Stated: AA and AG genotypes were collapsed using a dominant model to improve power because AA homozygotes were rare; future larger independent samples should compare all three genotypes directly.
  • Evident from the text: the study included only male European-ancestry participants and male-male pairs, limiting generalizability to females and other populations; it is a single-SNP candidate gene study without direct measurement of OXTR expression or function.

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

Integrity signals

Registry

Crossref · 10.3389/fnhum.2012.00004

Cites

48 of 51 references verified3 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 15 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Individuals homozygous for the G allele (GG) showed higher trust behavior than A allele carriers (AA/AG).

    “Individuals homozygous for the G allele (GG) showed higher trust behavior than individuals with A allele carriers (AA/AG).”
    • Also stated in: § Discussion · plain
      “In our study, participants with A allele carriers (AA/AG) showed lower trust behavior than participants homozygous for the G allele (GG).”
    Quote in the paperSubstantial claim
  • Findingown data

    Dispositional empathy was not associated with trust, risk, and trustworthy behaviors.

    “empathy was not associated with trust, risk, and trustworthy behaviors (rs < 0.11, Ps > 0.512).”
    Quote in the paperNot a substantial claim
  • Findingown data

    At the maximal trust level, the GG group transferred 14% more money than the AG/AA group.

    “The interaction effect was driven by an only significantly higher money transfer for the maximal trust level: the GG group transferred 14% more money than the AG/AA group [χ2 = 11.9, P < 0.0001, P corrected for multiple testing <0.001, Cohen’s d = 0.7”
    Quote in the paperSubstantial claim
  • Findingown data

    OXTR rs53576 genetic variation is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors in healthy male students.

    “Our results show that a common occurring genetic variation (rs53576) in the OXTR gene is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors.”
    • Also stated in: § Results · plain
      “The rs53576 SNP of the OXTR gene was specifically associated with trusting behavior rather than a general increase in risk or trustworthy behaviors.”
    • Also stated in: § Discussion · boosted
      “We demonstrated that a common occurring genetic variation (rs53576) in the OXTR gene is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors.”
    Quote in the paperSubstantial claim
  • Study design and conductown data

    The study had greater than 80% power to detect an association with moderate to large effect sizes (Cohen's d > 0.5).

    “A prospective power calculation showed that with the current sample size there was greater than 80% power to detect an association with moderate to large effects sizes (Cohen’s d > 0.5).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 7
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    In the trust experiment, there was a significant interaction between transfer level and genotype group on investor transfers, with no significant main effect of group.

    “For the investor’s transfers in the trust experiment, the ANOVA revealed no significant main effect for group [F(1,8) = 0.24, P = 0.636], but a significant main effect for transfer level [F(10,80) = 216.45, P < 0001], and a significant interaction effect for transfer level × group [F(10,80) = 6.02, P < 0.001].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the risk experiment, there was no significant effect of genotype group or interaction between transfer level and group on investor transfers.

    “For the investor’s transfers in the risk experiment, the ANOVA revealed only a significant main effect for transfer level [F(10,180) = 333.24, P < 0.001], but no significant main effect for group [F(1,18) = 1.65, P = 0.215], and no significant interaction effect for transfer level × group [F(10,180) = 1.83, P = 0.119; Figure 2B].”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The GG group had higher dispositional empathy than the AG/AA group.

    “Although the GG group had higher dispositional empathy than the AG/AA group [IRI: 2.7 ± 0.1, 2.5 ± 0.1; t(106) = 1.8, P = 0.039, one-sided, Cohen’s d = 2.0]”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Genotype groups did not differ on altruism, theory of mind ability, attachment styles, or personality styles.

    “Differences on psychological control measures (mean ± SD) were ruled out as alternative explanations, including altruism (RAS: 55.8 ± 1.4, 58.2 ± 1.9; P = 0.232), theory of mind ability (RMET: 72.5 ± 1.3, 72.8 ± 1.5%, P = 0.847), attachment styles (RSQ, secure: 3.3 ± 0.1, 3.2 ± 0.1; fearful: 2.7 ± 0.1, 2.9 ± 0.1; preoccupied: 2.9 ± 0.1, 2.8 ± 0.1; dismissing: 3.1 ± 0.1, 3.1 ± 0.1; Ps > 0.172)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the trust experiment, trustee back transfers showed no significant effect of genotype group or interactions with group.

    “but no significant main effect for group [F(1,18) = 0.48, P = 0.497], and no significant interaction effects for transfer level × group [F(10,180) = 1.30, P =0.231], back transfer level × group [F(30,540) = 1.28, P = 0.217], and transfer level × back transfer level × group [F(30,540) = 1.24, P = 0.269”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Investors in the trust and risk games faced the same objective risks, ensuring that trusting behavior could be distinguished from risk behavior.

    “Investors in the trust and risk games faced the same objective risks, ensuring that trusting behavior could be distinguished from risk behavior.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The overall genotyping accuracy was 100% with 100% completion.

    “The overall genotyping accuracy was 100% with 100% completion.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The enhancement of trust by exogenous oxytocin is driven by a higher frequency of money transfers for the maximal trust level.

    “However, a recent exogenous OXT study by Kosfeld et al. (2005) demonstrated that the enhancement of trust is driven by a higher frequency of money transfers for the maximal trust level.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kosfeld et al., 2005

      Not checked in the free run.

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

    Study design and conductown data

    The genotype distribution met Hardy-Weinberg Equilibrium expectations.

    “The genotype distribution (GG = 56, AG = 43, AA = 9) met Hardy-Weinberg Equilibrium expectations [χ2(1) = 0.03, P = 0.854]”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Oxytocin broadly influences socio-emotional behaviors.

    “Converging animal and human evidence reveals that OXT, a peptide that is produced in the hypothalamus and released in the brain and bloodstream that functions both as a hormone and neurotransmitter, broadly influences socio-emotional behaviors (Lee et al., 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lee et al., 2009

      Not checked in the free run.

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

    Interpretationreasoning

    The observed effect may reflect the impact of OXTR variants in LD with rs53576.

    “Because the molecular functionality of OXTR rs53576 is still unknown, our results cannot exclude the possibility that the observed effect may reflect the impact of OXTR variants in LD with rs53576.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The study hypothesized an association with one specific phenotype but not others based on previous published association studies.

    “Instead of conducting a “fishing expedition” in which a problem with spurious associations could arise (as in multiple SNP or GWAS studies), we hypothesized an association with one specific phenotype but not others based on previous published association studies (e.g., Rodrigues et al., 2009; Tost et al., 2010).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rodrigues et al., 2009

      Not checked in the free run.

    • cites Tost et al., 2010

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    The study was a theoretically driven, candidate gene investigation with reduced population stratification by testing only a Caucasian sample.

    “However, our study was a theoretically driven, candidate gene investigation with a reduction of population stratification by testing only a Caucasian sample.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    OXTR rs53576 impacts hypothalamic-limbic structure and function.

    “Our results are further complemented by evidence that OXTR rs53576 impacts both hypothalamic-limbic structure and function (Tost et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tost et al., 2010

      Not checked in the free run.

14 of 14

  • The paper relies on this without support.

    The link between OXTR rs53576 and human trust behavior is unknown.

    “Despite this accumulating evidence in support of a relationship between OXTR rs53576 and socio-emotional functions, its link to human trust behavior during social interaction remains unknown.”
1 of 1

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 A allele of rs53576 has been associated with a larger startle response, reduced emotion-reading abilities, reduced maternal sensitivity, fewer affiliative displays, reduced trust, increased hormonal and neurocardiac reactivity to social stress, and lower optimism, mastery, and self-esteem.

    “The A allele of rs53576 has been associated with a larger startle response and reduced emotion-reading abilities (Rodrigues et al., 2009), reduced maternal sensitivity (Bakermans-Kranenburg and van Ijzendoorn, 2008), fewer affiliative displays (Kogan et al., 2011), reduced trust (Krueger et al., 2012), increased hormonal and neurocardiac reactivity to social stress (Norman et al., 2012), and lower”

    From Integrative Approaches Utilizing Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to Autistic Social Dysfunction (2012) · cites this paper as Krueger et al., 2012

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Not confirmedF(10, 180) = 1.83reported p = .119 · recomputed p = .058

    “F(10,180) = 1.83, p = .119”

  • Not confirmedF(30, 540) = 1.28reported p = .217 · recomputed p = .149

    “F(30,540) = 1.28, p = .217”

  • Not confirmedF(30, 540) = 1.24reported p = .269 · recomputed p = .180

    “F(30,540) = 1.24, p = .269”

  • Consistentχ²(1) = 0.03reported p = .854 · recomputed p = .862

    “χ2(1) = 0.03, p = .854”

  • ConsistentF(2, 107) = 0.63reported p = .533 · recomputed p = .535

    “F(2,107) = 0.63, p = .533”

  • ConsistentF(2, 107) = 0.81reported p = .446 · recomputed p = .448

    “F(2,107) = 0.81, p = .446”

  • ConsistentF(1, 8) = 0.24reported p = .636 · recomputed p = .637

    “F(1,8) = 0.24, p = .636”

  • ConsistentF(10, 80) = 6.02reported p < .001 · recomputed p < .001

    “F(10,80) = 6.02, p < .001”

  • ConsistentF(10, 180) = 333.24reported p < .001 · recomputed p < .001

    “F(10,180) = 333.24, p < .001”

  • ConsistentF(1, 18) = 1.65reported p = .215 · recomputed p = .215

    “F(1,18) = 1.65, p = .215”

  • ConsistentF(10, 180) = 65.03reported p < .001 · recomputed p < .001

    “F(10,180) = 65.03, p < .001”

  • ConsistentF(30, 540) = 20.04reported p < .001 · recomputed p < .001

    “F(30,540) = 20.04, p < .001”

  • ConsistentF(300, 5400) = 20.84reported p < .001 · recomputed p < .001

    “F(300,5400) = 20.84, p < .001”

  • ConsistentF(1, 18) = 0.48reported p = .497 · recomputed p = .497

    “F(1,18) = 0.48, p = .497”

  • ConsistentF(10, 180) = 1.3reported p = .231 · recomputed p = .233

    “F(10,180) = 1.30, p = .231”

  • Consistentt(106) = 1.8reported p = .039 · recomputed p = .075

    “t(106) = 1.8, p = .039”

    The paper states a one-tailed test

16 of 16

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.

  • Comparison group for prosocial temperament changes within one sentence

    Minor

    The sentence says the difference was only between the two homozygote groups, GG and AA, but then describes the comparison as GG versus AG.

  • Empathy test switches from the stated two-tailed convention

    Minor

    The analysis section specifies two-tailed testing, but the reported empathy result explicitly uses a one-sided P value. This matters because the stated empathy difference is presented as significant under the one-sided test.

2 of 2

Cites

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Related

Authors
Krueger, F., Parasuraman, R., Iyengar, V., Thornburg, M., Weel, J., Lin, M., Clarke, E., McCabe, K., & Lipsky, R. H.
Affiliations
  • George Mason University (US)
  • Duke University (US)
  • Inova Health System (US)
Corresponding author
Krueger, Frank
ORCID
Venue
Frontiers in Human Neuroscience
Publisher
Frontiers Media SA
Published
2012
Volume
6
Pages
4-4
ISSN
1662-5161 (ISSN-L)
DOI
10.3389/fnhum.2012.00004
PMC
PMC3270329
OpenAlex
W2090409302
Semantic Scholar
5c9ce3b87d9b17c4fcf0e8c8a1464aff3bff067a
Cited by
207
References
50
Citations by year
2026: 5 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 4 · 2021: 14 · 2020: 42 · 2019: 21 · 2018: 13 · 2017: 15 · 2016: 18 · 2015: 18 · 2014: 18 · 2013: 13 · 2012: 6
FWCI
26.46
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Frontiers in Human Neuroscience (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Social Sciences › Safety Research › Experimental Behavioral Economics Studies
Keywords
oxytocin receptor, rs53576, single nucleotide polymorphisms, trust behavior, trust game, genetic variation, social-emotional behavior, gene-environment interaction

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