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

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dc.authoridMorosoli, Jose J./0000-0003-3959-403X
dc.authoridHeinrich, Joachim/0000-0002-9620-1629
dc.authoridAllegrini, Andrea/0000-0003-4048-4292
dc.authoridLu, Yi/0000-0001-9933-3654
dc.authoridJohansson, Stefan/0000-0002-2298-7008
dc.authoridDavey Smith, George/0000-0002-1407-8314
dc.authoridVuoksimaa, Eero/0000-0002-6534-3667
dc.contributor.authorIp, Hill F.
dc.contributor.authorvan der Laan, Camiel M.
dc.contributor.authorKrapohl, Eva M. L.
dc.contributor.authorBrikell, Isabell
dc.contributor.authorSanchez-Mora, Cristina
dc.contributor.authorNolte, Ilja M.
dc.contributor.authorSt Pourcain, Beate
dc.date.accessioned2024-09-29T16:01:01Z
dc.date.available2024-09-29T16:01:01Z
dc.date.issued2021
dc.departmentKarabük Üniversitesien_US
dc.description.abstractChildhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (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 AGG(overall). 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 r(g)= 0.46 between self- and teacher-assessment to r(g)d= 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 r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 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.en_US
dc.description.sponsorshipEuropean Union [602768]; Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies project (ACTION); MRC [MC_UU_00011/1] Funding Source: UKRIen_US
dc.description.sponsorshipWe 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. Cohortspecific acknowledgements and funding information may be found in the Supplementary text.en_US
dc.identifier.doi10.1038/s41398-021-01480-x
dc.identifier.issn2158-3188
dc.identifier.issue1en_US
dc.identifier.pmid34330890en_US
dc.identifier.scopus2-s2.0-85111704583en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1038/s41398-021-01480-x
dc.identifier.urihttps://hdl.handle.net/20.500.14619/5494
dc.identifier.volume11en_US
dc.identifier.wosWOS:000679719900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringernatureen_US
dc.relation.ispartofTranslational Psychiatryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectGenome-Wide Associationen_US
dc.subjectTrajectoriesen_US
dc.subjectHeritabilityen_US
dc.subjectAdolescenceen_US
dc.subjectDisorderen_US
dc.subjectBehavioren_US
dc.subjectOriginsen_US
dc.titleGenetic association study of childhood aggression across raters, instruments, and ageen_US
dc.typeArticleen_US

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