Pleiotropic Contribution of MECOM and AVPR1A to Aggression and Subcortical Brain Volumes
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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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Self-citation
- 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
- Publisher
- Frontiers Media SA
- Published
- 2018-04-03
- Volume
- 12
- Pages
- 61-61
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC5891600
- 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
- gold
- doi.org
- 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
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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