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Cited by 196Psychopathy, Forensic Psychiatry, Sexual OffendingGenetic Associations and EpidemiologyCrime Patterns and Interventions

Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior

Open access
Tielbeek, Jorim J., Johansson, Ada, Polderman, Tinca J. C., Rautiainen, Marja-Riitta, Jansen, Philip, Taylor, Michelle, Tong, Xiaoran, Lu, Qing +32 more·2017·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2017.3069PMC PMC6309228
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Abstract

Importance Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified.

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Crossref · 10.1001/jamapsychiatry.2017.3069

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

5 of 23 cited sources checked · 5 supported · 0 flagged

  • Premisenone given

    No specific causal genetic variants for antisocial behaviour have been identified.

    “Specific causal genetic variants have, however, not been identified.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Vassos, Collier, & Fazel, 2014 source
    • cites Kendler, 2013 source
  • Premisecitation

    A systematic review and meta-analysis found no significant overall association between previously reported candidate genes and aggression.

    “a systematic review and meta-analysis of the majority of published genetic association studies on aggression and violence failed to reveal a significant overall association between any of the previously reported candidate genes and aggression”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Vassos, Collier, & Fazel, 2014 source
  • Premisecitation

    Other published genome-wide association studies of antisocial phenotypes did not report genome-wide significant associations.

    “none of the other published GWAS studies Tielbeek et al. 2012(Tielbeek et al., 2012) (QIMR, N=4816, continuous measure of adult antisocial behaviour), Salvatore et al. 2015(Salvatore et al., 2015) (COGA, N=1379, continuous measure of adult antisocial behaviour, part of the present meta-analysis), Viding et al. 2010(Viding et al., 2010) (TEDS, N=1186 (Ncases=593), psychopathic tendencies) and Derr”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Tielbeek et al., 2012 source
    • cites Salvatore et al., 2015 source
    • cites Viding et al., 2010 source
  • Premisecitation

    One genome-wide association study of childhood conduct disorder in an American sample detected three genome-wide significant loci.

    “One study, carried out on childhood conduct disorder in an American sample (N=3963, including 872 cases and 3091 controls), detected three genome-wide significant loci”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites D. M. Dick et al., 2011 source
  • Findingown data

    Top signals were located differently across sex.

    “Top signals were located differently across sex, which is illustrated by the Miami plot in Figure 1 and Table S5.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 17
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingown data

    No significant genetic overlap was found with conduct disorder in YalePenn, although a nominal significant effect in the expected direction was found in the males-only analysis.

    “No significant genetic overlap was found with conduct disorder in YalePenn, although a nominal significant effect (p=.04, R2=.0022) in the expected direction was found in the males-only analysis”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Gene-based and gene-set analyses yielded no significant genes or gene-sets.

    “Gene-based and gene-set analyses yielded no significant genes (top gene= CENPI, p= 3.2 × 10-5, Table S3a-c, Figure S3) or gene-sets (top gene-set=‘Reactome cell communication’, p= 3.6 × 10-4, Table S3d).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The polygenic risk score analyses revealed low Nagelkerke's R2 estimates that did not exceed the Bonferroni corrected threshold for significance.

    “Nevertheless, the analyses revealed low Nagelkerke’s R2 estimates (R2=.0019 in the most optimal model) not exceeding the Bonferroni corrected threshold for significance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The Broad Antisocial Behaviour Consortium has genotypic and phenotypic data from 25,781 individuals across eight unique samples, making it the largest collective sample available for estimating genome-wide genetic variant effects on antisocial behaviour.

    “In total, BroadABC has genotypic and phenotypic data from 25,781 individuals across eight unique samples, making it the largest collective sample available to estimate the effects of genome wide genetic variants for ASB”
    • Also stated in: § Conclusions and Relevance · plain
      “The Broad Antisocial Behaviour Consortium entails the largest collaboration to date (total N=25,781) on the genetic architecture of antisocial behaviour”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The genomic inflation factors for the combined, male and female meta-analyses were 1.015, 1.012 and 1.001, respectively, which are as expected under a polygenic model.

    “The genomic inflation factors for the combined, male and female meta-analyses were 1.015, 1.012 and 1.001, respectively, which are as expected under a polygenic model given the current sample size, prevalence, and heritability of ASB”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The genetic effect from the females-only antisocial behaviour analysis significantly overlapped with genetic effects on conduct problems in MSUTR, but not with the sex-combined and males-only analyses.

    “we found that the genetic effect from the females-only ASB analysis significantly overlapped with genetic effects in the expected direction on conduct problems in MSUTR (p= .004, R2=.021 for the most optimal model, see Figure 2E), but not with the sex-combined and males-only analyses”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The genome-wide significance threshold was set at 1.67 x 10-8 because three meta-analyses were performed.

    “The genome-wide significance threshold was set at 1.67 x 10-8 as we performed three meta-analyses”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Polygenic risk score analysis based on a broad conceptualization of antisocial behaviour could reliably predict some variation in antisocial personality disorder in a forensic cohort, demonstrating that population-based genetic association studies can be informative for at-risk samples.

    “Polygenic risk score analysis, based on a broad conceptualization of ASB, could reliably predict some of the variation in antisocial personality disorder in a forensic cohort, demonstrating that population-based genetic association studies can also be informative for samples that are at-risk.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    There were no discrepancies between the results files of the two analysts at either the cohort level or the meta-analysis level.

    “There were no discrepancies between the results files of the two analysts at either the cohort level or the meta-analysis level.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    It cannot be ruled out that most of the genetic variance in antisocial behaviour is due to rare alleles.

    “although we cannot rule out that most of the genetic variance in ASB is due to rare alleles”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Previous meta-analytical genome-wide association studies successfully used a joint analysis approach and identified additional loci associated with depressive symptoms and neuroticism.

    “previous meta-analytical GWAS studies have successfully applied this joint analysis approach, by identifying additional loci associated with depressive symptoms and neuroticism”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Okbay, Baselmans, et al., 2016

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    Antisocial behaviour also correlates with reproductive traits, fitting the unified evolutionary theory proposed by Boutwell and others.

    “Strikingly, ASB also correlates with reproductive traits, thus fitting to the unified evolutionary theory that Boutwell and others proposed”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Boutwell et al., 2015 source

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

    Study design and conductnone given

    Quality control and meta-analysis of the genome-wide association summary results were performed by two independent analysts following a strict analysis protocol.

    “Quality control (QC) and meta-analysis of the GWA summary results were performed by two independent analysts (J.J.T. & A.J.), following a strict analysis protocol.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The measured SNPs accounted for 5% of the variance in antisocial behaviour, which is about 10% of the heritability estimated from family-based studies.

    “SNP heritability analyses demonstrated that the collective effect of the measured SNPs accounted for 5% of the variance, or 10% of the heritability of ˜50%, as estimated from family-based studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Antisocial behaviour is heritable and highly polygenic, and part of its genetic architecture is sex specific.

    “Our meta-analyses of diverse continuous measures of ASB showed that ASB is heritable and highly polygenic and suggests that part of the genetic architecture is sex specific.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Only polymorphisms with a total sample size greater than 10,000 across all samples and greater than 5,000 in sex-specific analyses were reported and interpreted.

    “We only reported and interpreted the results of polymorphisms with a total sample size greater than 10,000 (across all samples) and 5000 (sex-specific).”
    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

    We removed 2,134,049 SNPs due to insufficient total sample size, leaving 7,392,849 SNPs available for analyses.

    “We removed 2,134,049 SNPs due to insufficient total sample size (N < 10 000), resulting in 7,392,849 SNPs available for analyses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    All participants were recruited from different regions, making sample overlap highly unlikely.

    “All participants were recruited from different regions, thus making sample overlap highly unlikely.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Effect sizes were very small, indicating limited prediction accuracy and clinical utility for the current genome-wide association outcomes.

    “Nevertheless, effect sizes were very small, indicating limited prediction accuracy and clinical utility for the current GWAS outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    There are substantial differences in prevalence, age of onset, and severity of antisocial behaviour between males and females.

    “Given the substantial differences in prevalence, age of onset, and severity of ASB between males and females (Cale & Lilienfeld, 2002)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cale & Lilienfeld, 2002 source

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Genome-wide association analyses were performed at the cohort level according to a pre-specified analysis plan.

    “Genome-wide association analyses (GWA) were performed at the cohort level according to a pre-specified analysis plan (Standard Operating Procedures; SOP).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The genetic correlation analyses revealed a suggestive positive genetic correlation of antisocial behaviour with neuroticism, which is concordant with previous twin research demonstrating a shared genetic etiology of externalizing behaviour and negative emotionality.

    “Our genetic correlation analyses revealed a suggestive positive genetic correlation of ASB with neuroticism, which is concordant with previous twin research demonstrating a shared genetic etiology of externalizing behaviour and negative emotionality”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Singh & Waldman, 2010 source
22 of 22

  • The paper relies on this without support.

    Recent genome-wide association studies of other complex traits demonstrate that SNP heritability increases with greater sample sizes.

    “Recent GWAs on other complex traits such as height, BMI, and schizophrenia clearly demonstrated that with greater sample sizes the SNP h2 increases.”
1 of 1

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Authors
Tielbeek, J. J., Johansson, A., Polderman, T. J. C., Rautiainen, M.-R., Jansen, P., Taylor, M., Tong, X., Lu, Q., Burt, A. S., Tiemeier, H., Viding, E., Plomin, R., Martin, N. G., Heath, A. C., Madden, P. A. F., Montgomery, G., Beaver, K. M., Waldman, I., Gelernter, J., Kranzler, H. R., Farrer, L. A., Perry, J. R. B., Munafò, M., LoParo, D., Paunio, T., Tiihonen, J., Mous, S. E., Pappa, I., de Leeuw, C., Watanabe, K., Hammerschlag, A. R., Salvatore, J. E., Aliev, F., Bigdeli, T. B., Dick, D., Faraone, S. V., Popma, A., Medland, S. E., Posthuma, D., & for the Broad Antisocial Behavior Consortium collaborators
Affiliations
  • QIMR Berghofer Medical Research Institute (AU)
  • Åbo Akademi University (FI)
  • Amsterdam Neuroscience (NL)
  • University of Helsinki (FI)
  • Erasmus MC (NL)
  • University of Bristol (GB)
  • Michigan State University (US)
  • Department of Psychology, Michigan State University, East Lansing
  • University College London (GB)
  • Washington University in St. Louis (US)
  • Florida State University (US)
  • Emory University (US)
  • Veterans Health Administration (US)
  • Philadelphia VA Medical Center (US)
  • Boston University (US)
  • University of Cambridge (GB)
  • Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, England
  • University of Eastern Finland (FI)
  • Erasmus MC - Sophia Children’s Hospital (NL)
  • Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • Virginia Commonwealth University (US)
  • Department of African American Studies, Virginia Commonwealth University, Richmond
  • SUNY Upstate Medical University (US)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Corresponding author
Tielbeek, Jorim J.
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2017-12-01
Volume
74
Issue
12
Pages
1242
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2017.3069
PMC
PMC6309228
OpenAlex
W2762265603
Cited by
194
References
56
Citations by year
2026: 5 · 2025: 10 · 2024: 14 · 2023: 19 · 2022: 17 · 2021: 28 · 2020: 57 · 2019: 24 · 2018: 20
FWCI
34.18
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Explore Bristol Research (publishedVersion, other-oa)
  • VU Research Portal (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • UEF eRepo (University of Eastern Finland) (acceptedVersion)
  • Bristol Research (University of Bristol) (submittedVersion, other-oa)
  • UTUPub (University of Turku) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
  • Åbo Akademi University Research Portal (submittedVersion)
  • STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
  • WOS
Funders
  • Suomen Kulttuurirahasto
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO 480‐05‐003, 480- 05-003, VICI 453-14-005, 406-12-131, NWO VICI 453-14-005, 453-14-005)
  • Waldemar von Frenckells Stiftelse
  • National Institutes of Health
  • Medical Research Council (MC_UU_12015/2, MR/M021475/1, MC_PC_15018)
  • National Health and Medical Research Council (1103623)
  • National Institute on Alcohol Abuse and Alcoholism (F32AA022269, K01AA024152)
  • National Institute on Drug Abuse (K01DA033346)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Sociology and Political Science › Crime Patterns and Interventions
Keywords
antisocial behavior, genetic architecture, heritability, single nucleotide polymorphisms, genetic risk variants, pleiotropy, polygenic risk score, conduct problems, conduct disorder, substance dependence, educational attainment, European ancestry, psychiatric traits, candidate genes
MeSH terms
Adolescent, Adult, Antisocial Personality Disorder, Child, Environment, Female, Finland, Humans, Male, Middle Aged, Sex Factors, Genetic Variation, Conduct Disorder, Multifactorial Inheritance, Genome-Wide Association Study

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