Cited by 16Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologyNeuroendocrine regulation and behavior

Pleiotropic Contribution of MECOM and AVPR1A to Aggression and Subcortical Brain Volumes

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van Donkelaar, Marjolein M. J., Hoogman, Martine, Pappa, Irene, Tiemeier, Henning, Buitelaar, Jan K., Franke, Barbara, Bralten, Janita·2018·Frontiers in Behavioral Neuroscience

Abstract

Reactive and proactive subtypes of aggression have been recognized to help parse etiological heterogeneity of this complex phenotype. With a heritability of about 50%, genetic factors play a role in the development of aggressive behavior. Imaging studies implicate brain structures related to social behavior in aggression etiology, most notably the amygdala and striatum. This study aimed to gain more insight into the pathways from genetic risk factors for aggression to aggression phenotypes. To this end, we conducted genome-wide gene-based cross-trait meta-analyses of aggression with the volumes of amygdala, nucleus accumbens, and caudate nucleus to identify genes influencing both aggression and aggression-related brain volumes. We used data of large-scale genome-wide association studies of a) aggressive behavior in children and adolescents (EAGLE, N=18,988) and b) Magnetic Resonance Imaging (MRI)-based volume measures of aggression-relevant subcortical brain regions (ENIGMA2, N=13,171). Second, the identified genes were further investigated in a sample of healthy adults (mean age (SD)=25.28 (4.62) years; 43% male) who had genome-wide genotyping data and questionnaire data on aggression subtypes available (BIG, N=501) to study their effect on reactive and proactive subtypes of aggression. Our meta-analysis identified two genes, MECOM and AVPR1A, significantly associated with both aggression risk and nucleus accumbens (MECOM) and amygdala (AVPR1A) brain volume. Subsequent in-depth analysis of these genes in healthy adults (BIG), including sex as an interaction term in the model, revealed no significant subtype-specific gene-wide associations. Using cross-trait meta-analysis of brain measures and psychiatric phenotypes, this study generated new hypotheses about specific links between genes, the brain, and behavior. Results indicate that MECOM and AVPR1A may exert an effect on aggression through mechanisms involving nucleus accumbens and amygdala volumes, respectively.

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  1. Baron R. A. Deborah D. S. (1994). Human Aggression. New York, NY: Plenum Press.

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Authors
van Donkelaar, M. M. J., Hoogman, M., Pappa, I., Tiemeier, H., Buitelaar, J. K., Franke, B., & Bralten, J.
Affiliations
  • Radboud University Nijmegen (NL)
  • Erasmus MC (NL)
Corresponding author
Bralten, Janita
Venue
Frontiers in Behavioral Neuroscience
Published
2018-04-03
Volume
12
Pages
61-61
ISSN
1662-5153 (ISSN-L)
OpenAlex
W2796436168
Cited by
16
References
78
Citations by year
2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 1
FWCI
0.91
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • VU Research Portal (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (433-09-229, 016-130-669)
  • Seventh Framework Programme (602805, 602450, 278948)
  • Horizon 2020 (643051, 667302)
  • Foundation for the National Institutes of Health (U54 EB020403)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
aggression, reactive aggression, proactive aggression, MECOM, AVPR1A, amygdala volume, nucleus accumbens, caudate nucleus, subcortical volume, gene-brain-behavior relationship, aggression subtypes, sex differences

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