Genetic association study of childhood aggression across raters, instruments, and age

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  • dc.contributor.author Ip, Hill F.
  • dc.contributor.author Vilor Tejedor, Natàlia, 1988-
  • dc.contributor.author Alemany, Silvia
  • dc.contributor.author Sunyer Deu, Jordi
  • dc.contributor.author Boomsma, Dorret I.
  • dc.date.accessioned 2021-12-03T06:52:34Z
  • dc.date.available 2021-12-03T06:52:34Z
  • dc.date.issued 2021
  • dc.description.abstract Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
  • dc.description.sponsorship We very warmly thank all participants, their parents, and teachers for making this study possible. The project was supported by the “Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies” project (ACTION). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no 602768. Cohort-specific acknowledgements and funding information may be found in the Supplementary text.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Ip HF, van der Laan CM, Krapohl EML, Brikell I, Sánchez-Mora C, Nolte IM et al. Genetic association study of childhood aggression across raters, instruments, and age. Transl Psychiatry. 2021;11(1):413. DOI: 10.1038/s41398-021-01480-x
  • dc.identifier.doi http://dx.doi.org/10.1038/s41398-021-01480-x
  • dc.identifier.issn 2158-3188
  • dc.identifier.uri http://hdl.handle.net/10230/49140
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Transl Psychiatry. 2021;11(1):413
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602768
  • dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Genomics
  • dc.subject.keyword Human behaviour
  • dc.title Genetic association study of childhood aggression across raters, instruments, and age
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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