Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression
Open accessAbstract
A large number of candidate gene studies for aggression and violence have been conducted. Successful identification of associations between genetic markers and aggression would contribute to understanding the neurobiology of antisocial behavior and potentially provide useful tools for risk prediction and therapeutic targets for high-risk groups of patients and offenders. We systematically reviewed the literature and assessed the evidence on genetic association studies of aggression and related outcomes in order to provide a field synopsis. We searched PubMed and Huge Navigator databases and sought additional data through reviewing reference lists and correspondence with investigators. Genetic association studies were included if outcome data on aggression or violent behavior either as a binary outcome or as a quantitative trait were provided. From 1331 potentially relevant investigations, 185 studies constituting 277 independent associations on 31 genes fulfilled the predetermined selection criteria. Data from variants investigated in three or more samples were combined in meta-analyses and potential sources of heterogeneity were investigated using subgroup analyses. In the primary analyses, which used relaxed inclusion criteria, we found no association between any polymorphism analyzed and aggression at the 5% level of significance. Subgroup analyses, including by severity of outcome, age group, characteristics of the sample and ethnicity, did not demonstrate any consistent findings. Current evidence does not support the use of such genes to predict dangerousness or as markers for therapeutic interventions.
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No specific causal genetic variants for antisocial behaviour have been identified.
“Specific causal genetic variants have, however, not been identified.”
From Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior (2017) · cites this paper as Vassos, Collier, & Fazel, 2014
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”
From Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior (2017) · cites this paper as Vassos, Collier, & Fazel, 2014
GWAS of aggression have been underpowered to detect common variants of small penetrance associated with complex phenotypes.
“Genome-wide association studies (GWAS) of aggression have been underpowered to detect common variants of small penetrance associated with complex phenotypes [11, 12].”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [12]
The largest meta-analysis of candidate genes for aggression performed to date did not find any significant association.
“However, the largest meta-analysis of candidate genes performed to date [12] did not find any significant association.”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [12]
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Fernàndez‐Castillo, N., & Cormand, B. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32419 · Cited by 87 · see citing works
“We selected 268 potential articles within those dates and added 263 articles from a previous review [Gunter et al., 2010] and from a meta-analysis [Vassos et al., 2014].”
BackgroundMethodResultInfluentialResearch Design in Clinical Psychology
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Molecular genetics and antisocial behavior: Where do we stand?
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“These authors did not identify any major effect by single genes on aggression, and concluded that the candidate gene approach has not succeeded in identifying genes associated with aggression and violence.(76) However, they did not include G E studies in their analysis, as they examined only the main effects of single…”
BackgroundLi, N.-X., Hu, Y.-R., Chen, W.-N., & Zhang, B. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.09.041 · Cited by 72 · see citing works
The forensic use of behavioral genetics in criminal proceedings: Case of the MAOA-L genotype
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Biological Aspects of Aggression and Violence in Schizophrenia
Cho, W., Shin, W., An, I., Bang, M., Cho, D., & Lee, S.-H. (2019) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2019.17.4.475 · Cited by 63 · see citing works
“The most recent meta-analysis found no association between any polymorphism and aggression and did not provide any evidence supporting the use of genetic markers for risk prediction and management of aggression in schizophrenia patients [71].”
BackgroundGenome‐wide analyses of aggressiveness in attention‐deficit hyperactivity disorder
Brevik, E. J., van Donkelaar, M. M. J., Weber, H., Sánchez‐Mora, C., Jacob, C., Rivero, O., Kittel‐Schneider, S., Garcia‐Martínez, I., Aebi, M., van Hulzen, K., et al. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32434 · Cited by 57 · see citing works
“Thus, the overall genetic architecture of ADHD and/or aggression remains largely unknown and warrants studies using a hypothesis-free approach [Vassos et al., 2014].”
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“The available genome-wide association studies (GWAS) on adulthood antisocial behaviours have thus far been too small and heterogeneous to yield any robust findings and comprehensive meta-analyses have failed to identify a single significant polymorphism associated with aggression (34, 35).”
Self-citationJaniri, D., Rossi, P. D., Kotzalidis, G. D., Girardi, P., Koukopoulos, A. E., Reginaldi, D., Dotto, F., Manfredi, G., Jollant, F., Gorwood, P. A. P. M., et al. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.05.009 · Cited by 58 · see citing works
“Aggressiveness is multidimensional and largely influenced by genetic factors [31].”
BackgroundA neurodevelopmental perspective on male violence
Raine, A. (2018) · Infant Mental Health Journal · doi:10.1002/imhj.21761 · Cited by 56 · see citing works
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Malki, K., Du Rietz, E., Crusio, W. E., Pain, O., Paya‐Cano, J., Karadaghi, R. L., Sluyter, F., de Boer, S. F., Sandnabba, K., Schalkwyk, L. C., et al. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32451 · Cited by 52 · see citing works
“However, these findings often show small effect sizes and fail to replicate [Vassos et al., 2014].”
ResultTielbeek, J. J., Linnér, R. K., Beers, K., Danielle Posthuma, B., Popma, A., & Polderman, T. J. C. (2016) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32442 · Cited by 52 · see citing works
Genetic architecture for human aggression: A study of gene–phenotype relationship in OMIM
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Genetic and Gene–Environment Influences on Disruptive Behavior Disorders
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The interaction of biopsychological and socio-environmental influences on criminological outcomes
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Aggression in non‐human vertebrates: Genetic mechanisms and molecular pathways
Freudenberg, F., Gutiérrez, H. C., Post, A. M., Reif, A., & Norton, W. (2015) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32358 · Cited by 44 · see citing works
“However, as a caveat, a recent meta-analysis failed to find significant associations between candidate genes and human aggression [Vassos et al., 2013].”
ResultAebi, M., van Donkelaar, M. M. J., Poelmans, G., Buitelaar, J. K., Sonuga-Barke, E. J. S., Stringaris, A. K., Faraone, S. V., Franke, B., Steinhausen, H., & van Hulzen, K. J. E. (2015) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32346 · Cited by 45 · see citing works
“A recent metaanalysis showed a significant association of the short allele of the polymorphic region (5-HTTLPR) in the promoter region of the serotonin transporter gene 5-HTT/SLC6A4 with antisocial behaviors (including aggression) [Ficks and Waldman, 2014], although evidence for this association is conflicting [Vassos…”
BackgroundResultMentis, A. A., Dardiotis, E., Katsouni, E., & Chrousos, G. P. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01257-2 · Cited by 45 · see citing works
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Overlapping cytokines in H. pylori infection and gastric cancer: A tandem meta-analysis
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Psychiatric Genetics in Child Custody Proceedings: Ethical, Legal, and Social Issues
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Single-case experimental research designs.
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Neurobiological Correlates in Forensic Assessment: A Systematic Review
van der Gronde, T., Kempes, M. M., van El, C. G., Rinne, T., & Pieters, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110672 · Cited by 39 · see citing works
“[7,69,76,95,101,103,108,110,126] Violence should be considered as the end product of a chain of events over the course of a person’s development, during which risks accumulate and potentially reinforce each other.”
BackgroundMethodInfluentialFond, G. B., Bennabi, D., Haffen, É., Brunel, L., Micoulaud‐Franchi, J., Loundou, A., Lançon, C., Llorca, P., Auquier, P., & Boyer, L. (2016) · Scientific Reports · doi:10.1038/srep19847 · Cited by 38 · see citing works
Aggression and polymorphisms in AR, DAT1, DRD2 and COMT genes in Datoga pastoralists of Tanzania
Butovskaya, M., Vasilyev, V. A., Lazebny, O. E., Suchodolskaya, E. M., Shibalev, D. V., Куликов, А. М., Карелин, Д. В., Burkova, V. N., Mabulla, A. Z. P., & Рысков, А. П. (2013) · Scientific Reports · doi:10.1038/srep03148 · Cited by 36 · see citing works
Genes and Gene Networks Implicated in Aggression Related Behaviour
Malki, K., Pain, O., Du Rietz, E., Tosto, M. G., Paya-Cano, J., Sandnabba, K. N., de Boer, S., Schalkwyk, L. C., & Sluyter, F. (2014) · neurogenetics · doi:10.1007/s10048-014-0417-x · Cited by 33 · see citing works
“As a result, there has been a considerable research effort to identify genetic variation associated with aggressive behaviour [5].”
BackgroundCecil, C. A. M., Walton, E., Pingault, J., Provençal, N., Pappa, I., Vitaro, F., Côté, S. M., Szyf, M., Tremblay, R. E., Tiemeier, H. W., et al. (2018) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32689 · Cited by 29 · see citing works
Physical and verbal aggressive behavior and COMT genotype: Sensitivity to the environment
Tuvblad, C., Narusyte, J., Comasco, E., Andershed, H., Andershed, A., Colins, O. F., Fanti, K. A., & Nilsson, K. W. (2016) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32430 · Cited by 28 · see citing works
“Finally, there is a debate about the validity of candidate gene and cG E studies and which study designs in genetics that should be preferred [Duncan and Keller, 2011; Iofrida et al., 2014; Keller, 2014; Vassos et al., 2014].”
BackgroundNeural networks underlying trait aggression depend on MAOA gene alleles
Klasen, M., Wolf, D., Eisner, P. D., Habel, U., Repple, J., Vernaleken, I., Schlüter, T., Eggermann, T., Zerres, K., Zepf, F. D., et al. (2017) · Brain Structure and Function · doi:10.1007/s00429-017-1528-6 · Cited by 27 · see citing works
“This absence of a pure genotype effect on aggression is in line with previous findings (Vassos et al. 2013).”
ResultSerotonin and aggressive behaviour in children and adolescents: a systematic review
Runions, K., Morandini, H. A. E., Rao, P., Wong, J. W. Y., Kolla, N. J., Pace, G., Mahfouda, S., Hildebrandt, C. S., Stewart, R., & Zepf, F. D. (2018) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12986 · Cited by 26 · see citing works
“One recent meta-analysis of the role of these genetic variants found that none of the pooled effects of these genes were significantly associated with human aggression (15).”
BackgroundManchia, M., Comai, S., Pinna, M., Pinna, F., Fanos, V., Denovan‐Wright, E. M., & Carpiniello, B. (2019) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.004 · Cited by 26 · see citing works
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“For type of index offenses, only violent offenses were included as covariate as this type of offense is related to aggression (Vassos et al. 2014).”
BackgroundCortico‐limbic connectivity in MAOA‐L carriers is vulnerable to acute tryptophan depletion
Eisner, P. D., Klasen, M., Wolf, D., Zerres, K., Eggermann, T., Eisert, A., Zvyagintsev, M., Sarkheil, P., Mathiak, K. A., Zepf, F. D., et al. (2016) · Human Brain Mapping · doi:10.1002/hbm.23475 · Cited by 23 · see citing works
“Though several studies replicated the association between antisocial behavior and carriers of the MAOA-L gene, a direct link has not been reported consistently [for a review, see Vassos et al., 2014].”
BackgroundBehavioral Genetics in Criminal and Civil Courts
Sabatello, M., & Appelbaum, P. S. (2017) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000141 · Cited by 27 · see citing works
Monoamine oxidase and agitation in psychiatric patients
Perković, M. N., Štrac, D. Š., Erjavec, G. N., Uzun, S., Podobnik, J., Kozumplik, O., Vlatković, S., & Pivac, N. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.02.002 · Cited by 23 · see citing works
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“The results, however, are inconsistent, and recent meta-analyses did not resolve the involvement of this polymorphism in aggressiveness [29, 30].”
ResultThe biology of aggressive behavior in bipolar disorder: A systematic review
Fico, G., Anmella, G., Pacchiarotti, I., Verdolini, N., Sagué‐Vilavella, M., Corponi, F., Manchia, M., Vieta, E., & Murru, A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.09.015 · Cited by 21 · see citing works
Aggressiveness and violence in psychiatric patients: a clinical or social paradigm?
Mauri, M. C., Cirnigliaro, G., Pace, C. D., Paletta, S., Reggiori, A., Altamura, C. A., & Dell’Osso, B. M. (2019) · CNS Spectrums · doi:10.1017/s1092852918001438 · Cited by 20 · see citing works
“Violence is responsible for 5% of all disability and 3% of health spending in the USA.(3) According to the Italian National Statistical Institute (ISTAT), during the 2008– 2009 period, 5.”
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“A future genetic and epigenetic study of additional variants in miRNA genes involved in brain function, in samples of healthy subjects and patients with neuropsychiatric disorders, could identify novel candidates for aggressiveness [12,14,20,44,45].”
BackgroundMethodRuisch, I. H., Dietrich, A., Glennon, J. C., Buitelaar, J. K., & Hoekstra, P. J. (2019) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-018-0964-5 · Cited by 19 · see citing works
Neurobiología de la agresión y la violencia
Ortega‐Escobar, J., & Alcázar‐Córcoles, M. Á. (2016) · Anuario de Psicología Jurídica · doi:10.1016/j.apj.2016.03.001 · Cited by 19 · see citing works
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“Although a moderate number of studies has been conducted, a meta-analysis of individual candidate variants did not reveal any significant associations with aggressive behavior (Vassos et al., 2014).”
Manchia, M., Booij, L., Pinna, F., Wong, J. W. Y., Zepf, F. D., & Comai, S. (2019) · Comprehensive approach to psychiatry · doi:10.1007/978-3-030-33188-7_2 · Cited by 17 · see citing works
A Systematic Appraisal of Field Synopses in Genetic Epidemiology: A HuGE Review
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“Vassos, 2014 (49) RE ≥3 different data sets per variant Ethnicity, disease characteristics, population characteristics Study characteristics Q, I 2 No Venice criteria Begg’s test, Egger’s test”
BackgroundRare copy number variation in extremely impulsively violent males
Vevera, J., Zarrei, M., Hartmannová, H., Jedličková, I., Mušálková, D., Přistoupilová, A., Oliveriusová, P., Trešlová, H., Nosková, L., Hodaňová, K., et al. (2019) · Genes, Brain and Behavior · doi:10.1111/gbb.12536 · Cited by 15 · see citing works
Causes and cures II: The biology of violence
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Aggressive Behavior and Social Stress
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Violence exposure in an urban city: A GxE interaction with aggressive and impulsive behaviors
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COMTVal158Met moderates the link between rank and aggression in a non‐human primate
Gutleb, D. R., Roos, C., Noll, A., Ostner, J., & Schülke, O. (2017) · Genes Brain & Behavior · doi:10.1111/gbb.12443 · Cited by 14 · see citing works
“promising candidate gene for the regulation of neural processes leading to aggressive behavior.(5,22,23)”
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Physiological and health-related correlates of the narcissistic personality
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“Bad genes” & criminal responsibility
González-Tapia, M. I., & Obsuth, I. (2015) · International Journal of Law and Psychiatry · doi:10.1016/j.ijlp.2015.01.022 · Cited by 13 · see citing works
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The Return of Lombroso? Ethical Aspects of (Visions of) Preventive Forensic Screening
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“…and twin studies have shown that hereditary factors explain about 65% of the difference in risk for aggressive antisocial behaviour (Burt, 2009)), it has proved exceedingly difficult to pin precise behaviour patterns on specific molecular genetic variants (Lee et al., 2013; Vassos et al., 2014).”
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Comparative mRNA analysis of behavioral and genetic mouse models of aggression
Malki, K., Tosto, M. G., Pain, O., Sluyter, F., Mineur, Y. S., Crusio, W. E., de Boer, S., Sandnabba, K. N., Kesserwani, J., Robinson, E., et al. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32424 · Cited by 10 · see citing works
“Behavior-genetic studies have systematically reported moderate heritability estimates of aggression, with different measures of aggression resulting in estimates varying from 22% to 51% [Miles and Carey, 1997; Seroczynski et al., 1999; Vassos et al., 2014].”
BackgroundGenetic and Genomic Basis of Aggressive Behavior
Novoselskaya-Dragovich, A. Y., & Borinskaya, S. A. (2019) · Russian Journal of Genetics · doi:10.1134/s1022795419090059 · Cited by 10 · see citing works
Shedding Light on Antisocial Behavior Through Genetically Informed Research
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“However, the role of single genetic variants in human ASB remains uncertain, with some meta-analyses finding significant associations (Ficks & Waldman, 2014), and others finding none (Vassos et al., 2014).”
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“We considered values of I(2) [ 50 % as indicative of large heterogeneity [44].”
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“Common polymorphisms in several candidate genes have been reported in association with childhood aggression and externalizing (Volavka et al. 2004; Oades et al. 2008; Takahashi et al. 2012), but these effects have not held up after meta-analysis (Vassos et al. 2014).”
BackgroundVaht, M., Laas, K., Noèlia Fernàndez-castillo, A., Kurrikoff, T., Kanarik, M., Faraone, S. V., Tooding, L., Veidebaum, T., Franke, B., Reif, A., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.501847 · Cited by 8 · see citing works
“Several variants of RBFOX1 have been associated with aspects of aggressiveness in a number of GWASs (23).”
BackgroundInfluentialMechanisms in the relation between GABRA2 and adolescent externalizing problems
Wang, F. L., Chassin, L., Geiser, C., & Lemery‐Chalfant, K. (2015) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0703-7 · Cited by 8 · see citing works
“In testing these questions, it is important to acknowledge that a limitation of the candidate gene literature is the lack of replicability across studies [70].”
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Interventions to Reduce Recidivism in Adult Violent Offenders
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Anger Treatment with Violent Offenders
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- Authors
- Vassos, E., Collier, D. A., & Fazel, S.
- Affiliations
- King's College London (GB)
- University of Oxford (GB)
- Corresponding author
- Vassos, E
- Venue
- Molecular Psychiatry
- Published
- 2013-04-02
- Volume
- 19
- Issue
- 4
- Pages
- 471-477
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3965568
- OpenAlex
- W2146296397
- Cited by
- 234
- References
- 64
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 37 · 2020: 51 · 2019: 20 · 2018: 15 · 2017: 17 · 2016: 28 · 2015: 24 · 2014: 12 · 2013: 2
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (095806)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- aggression, violence, candidate gene association, genetic association, antisocial behavior, genetic polymorphism, risk prediction, subgroup heterogeneity
- MeSH terms
- Aggression, Humans, Violence, Databases, Factual, Genetic Association Studies
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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