6533b7d1fe1ef96bd125ce1d

RESEARCH PRODUCT

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

Nicholas G. MartinS. Alexandra BurtLouise ArseneaultFazil AlievLuke M. EvansHill F. IpBeate St PourcainBeate St PourcainBeate St PourcainMichel G. NivardWilliam E. CopelandRebecca K. VindingScott GordonKoen BolhuisChristian J. HopferGun Peggy KnudsenStefan JohanssonAvshalom CaspiAvshalom CaspiRichard BorderChandra A. ReynoldsPål R. NjølstadLiisa Keltikangas-järvinenDorret I. BoomsmaDorret I. BoomsmaKlaus BønnelykkeTeemu PalviainenMarta RibasésMarta RibasésAlina RodriguezAlina RodriguezCatharina A. HartmanIlkka SeppäläChristel M. MiddeldorpChristel M. MiddeldorpRosa BoschRosa BoschJan HaavikJan HaavikGail M. WilliamsAndrea G. AllegriniRuth KsJohn R. B. PerryHadi ZafarmandChang JiangChang JiangElizabeth J. CostelloCamiel M. Van Der LaanOlli T. RaitakariOlli T. RaitakariMiquel CasasIsabell BrikellWilliam G. IaconoJaakko KaprioJohn K. HewittAndrew C. HeathEero VuoksimaaXiaoran TongXiaoran TongGemma EspañolErik A. EhliRichie PoultonGareth E. DaviesAlbertine J. OldehinkelHans BisgaardNaomi R. WrayTed Reichborn-kjennerudTed Reichborn-kjennerudRobert PlominMichael C. StallingsQing LuQing LuJackob M. NajmanDaniel E. AdkinsYi LuHarold SniederSally J. WadsworthAlexander NeumannAlexander NeumannAlexandra HavdahlKaren SugdenKelly L. KlumpAndrew SmolenHenrik LarssonHenrik LarssonToos C. E. M. Van BeijsterveldtKenneth KrauterTarunveer S. AhluwaliaTarunveer S. AhluwaliaTellervo KorhonenAndrey A. ShabalinJoachim HeinrichJoachim HeinrichAnke R. HammerschlagAnke R. HammerschlagAnke R. HammerschlagShelby MarringtonLærke SassPamela A. F. MaddenHenning TiemeierHenning TiemeierTanja VrijkottePaul LichtensteinTerho LehtimäkiVille KarhunenCristina Sánchez-moraCristina Sánchez-moraRobin P. CorleyAnna A. E. VinkhuyzenRichard J. RosePer MagnusSabrina LlopIlja M. NolteS.a. BrownChristian HakulinenAnjali K. HendersMarie StandlSilvia AlemanyGretchen R.b. SaundersJouke-jan HottengaEveline L. De ZeeuwMeike BartelsMeike BartelsElisabeth ThieringJosé J. MorosoliFiona A. HagenbeekLaura Pulkki-råbackFrank C. VerhulstFrank C. VerhulstMartin A. KennedyCraig E. PennellEva KrapohlKaili RimfeldTetyana ZayatsTetyana ZayatsTetyana ZayatsLucía Colodro-condeJudith B.m. EnsinkAndré G. UitterlindenNatalia Vilor-tejedorFelix R. DayJennifer R. HarrisGeorge Davey SmithQi ChenSebastian LundströmMarjo-riitta JärvelinMarjo-riitta JärvelinAlyce M. WhippKatrina L. GrasbyL. John HorwoodJohn PearsonJudy L. SilbergPaula RoviraPaula RoviraHermine H. MaesCarol A. WangRoseann E. PetersonTamara L. WallAndrew J. O. WhitehouseMaria-josé Lopez-espinosaNajaf AminJess TyrrellDanielle M. DickSarah E. MedlandAllison L. MillerØYvind HelgelandJosep Antoni Ramos QuirogaJoseph M. BodenAbdullah MamunJames ScottJames ScottMaría Soler ArtigasMaría Soler ArtigasJoseph A. PrinzLindon J. EavesTerrie E. MoffittTerrie E. MoffittMatt McgueJordi SunyerJoanna MartinJoanna Martin

subject

0301 basic medicineDISORDER/45/43Genome-wide association study3124 Neurology and psychiatry0302 clinical medicineChildPsychiatry0303 health sciences:trastornos mentales [PSIQUIATRÍA Y PSICOLOGÍA]HERITABILITYMental DisordersCognitionGenomicsExplained variationJustice and Strong InstitutionsAggressionPsychiatry and Mental healthMeta-analysisADOLESCENCEChild Preschool:conducta y mecanismos de la conducta::conducta::síntomas conductuales::agresión [PSIQUIATRÍA Y PSICOLOGÍA]/631/208/212/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemaleBiological psychiatrymedicine.symptomLife Sciences & Biomedicine:Investigative Techniques::Genetic Techniques::Genetic Association Studies [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT]BEHAVIORRC321-571Childhood aggressionClinical psychologySDG 16 - PeaceAdolescent:Mental Disorders [PSYCHIATRY AND PSYCHOLOGY]Neurosciences. Biological psychiatry. NeuropsychiatrySingle-nucleotide polymorphismBiology3121 Internal medicineMalalties mentals - Aspectes genèticsGenetic correlationArticle1117 Public Health and Health ServicesCellular and Molecular Neuroscience03 medical and health sciences/631/477/2811SDG 3 - Good Health and Well-beingHuman behaviourmedicineSNPHumansGENOME-WIDE ASSOCIATIONBiological PsychiatryGenetic Association Studies030304 developmental biologyGenetic associationRetrospective Studies:técnicas de investigación::técnicas genéticas::estudios de asociación genética [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS]Science & TechnologyAggressionSDG 16 - Peace Justice and Strong InstitutionsInfant:Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Aggression [PSYCHIATRY AND PSYCHOLOGY]1103 Clinical SciencesAgressivitat en els infantsHeritability/dk/atira/pure/sustainabledevelopmentgoals/peace_justice_and_strong_institutions030104 developmental biology1701 PsychologyORIGINSResearch Programm of Donders Centre for Neuroscience3111 BiomedicineTRAJECTORIES030217 neurology & neurosurgeryDemographyGenome-Wide Association Study

description

AbstractChildhood 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 $$\left| {r_g} \right|$$ r g : 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 $$\left| {r_g} \right|$$ 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.

10.1038/s41398-021-01480-xhttps://trepo.tuni.fi/handle/10024/133797