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Ip, H.F.* ; van der Laan, C.M.* ; Krapohl, E.M.L.* ; Brikell, I.* ; Sánchez-Mora, C.* ; Nolte, I.M.* ; St Pourcain, B.* ; Bolhuis, K.* ; Palviainen, T.* ; Zafarmand, H.* ; Colodro-Conde, L.* ; Gordon, S.* ; Zayats, T.* ; Aliev, F.* ; Jiang, C.* ; Wang, C.A.* ; Saunders, G.* ; Karhunen, V.* ; Hammerschlag, A.R.* ; Adkins, D.E.* ; Border, R.* ; Peterson, R.E.* ; Prinz, J.A.* ; Thiering, E. ; Seppälä, I.* ; Ahluwalia, T.S.* ; Day, F.R.* ; Hottenga, J.J.* ; Allegrini, A.G.* ; Rimfeld, K.* ; Chen, Q.* ; Lu, Y.* ; Martin, J.* ; Soler Artigas, M.* ; Rovira, P.* ; Bosch, R.* ; Español, G.* ; Ramos Quiroga, J.A.* ; Neumann, A.* ; Ensink, J.* ; Grasby, K.* ; Morosoli, J.J.* ; Tong, X.* ; Marrington, S.* ; Middeldorp, C.* ; Scott, J.G.* ; Vinkhuyzen, A.A.* ; Shabalin, A.A.* ; Corley, R.* ; Evans, L.M.* ; Sugden, K.* ; Alemany, S.* ; Sass, L.* ; Vinding, R.* ; Ruth, K.* ; Tyrrell, J.* ; Davies, G.E.* ; Ehli, E.A.* ; Hagenbeek, F.A.* ; De Zeeuw, E.* ; Van Beijsterveldt, T.C.E.M.* ; Larsson, H.* ; Snieder, H.* ; Verhulst, F.C.* ; Amin, N.* ; Whipp, A.M.* ; Korhonen, T.* ; Vuoksimaa, E.* ; Rose, R.J.* ; Uitterlinden, A.G.* ; Heath, A.C.* ; Madden, P.* ; Haavik, J.* ; Harris, J.R.* ; Helgeland, Ø.* ; Johansson, S.* ; Knudsen, G.P.S.* ; Njolstad, P.R.* ; Lu, Q.* ; Rodriguez, A.* ; Henders, A.K.* ; Mamun, A.* ; Najman, J.M.* ; Brown, S.* ; Hopfer, C.J.* ; Krauter, K.* ; Reynolds, C.* ; Smolen, A.* ; Stallings, M.C.* ; Wadsworth, S.* ; Wall, T.L.* ; Silberg, J.L.* ; Miller, A.* ; Keltikangas-Järvinen, L.* ; Hakulinen, C.* ; Pulkki-Råback, L.* ; Havdahl, A.* ; Magnus, P.* ; Raitakari, O.T.* ; Perry, J.R.B.* ; Llop, S.* ; Lopez-Espinosa, M.J.* ; Bønnelykke, K.* ; Bisgaard, H.* ; Sunyer, J.* ; Lehtimäki, T.* ; Arseneault, L.* ; Standl, M. ; Heinrich, J. ; Boden, J.M.* ; Pearson, J.F.* ; Horwood, L.J.* ; Kennedy, M.* ; Poulton, R.* ; Eaves, L.J.* ; Maes, H.H.* ; Hewitt, J.K.* ; Copeland, W.E.* ; Costello, E.J.* ; Williams, G.M.* ; Wray, N.R.* ; Jarvelin, M.R.* ; McGue, M.* ; Iacono, W.G.* ; Caspi, A.* ; Moffitt, T.E.* ; Whitehouse, A.J.* ; Pennell, C.E.* ; Klump, K.L.* ; Burt, S.A.* ; Dick, D.M.* ; Reichborn-Kjennerud, T.* ; Martin, N.G.* ; Medland, S.E.* ; Vrijkotte, T.* ; Kaprio, J.* ; Tiemeier, H.* ; Davey Smith, G.* ; Hartman, C.A.* ; Oldehinkel, A.J.* ; Casas, M.* ; Ribasés, M.* ; Lichtenstein, P.* ; Lundstrom, S.* ; Plomin, R.* ; Bartels, M.* ; Nivard, M.G.* ; Boomsma, D.I.*

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

Transl. Psychiatry 11:413 (2021)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genome-wide Association; Trajectories; Heritability; Adolescence; Disorder; Behavior; Origins
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 2158-3188
e-ISSN 2158-3188
Zeitschrift Translational Psychiatry
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: 413 Supplement: ,
Verlag Nature Publishing Group
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504000-008
Förderungen "Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies" project (ACTION)
European Union
DOI 10.1038/s41398-021-01480-x
WOS ID WOS:000679719900001
Scopus ID 85111704583
PubMed ID 34330890
Erfassungsdatum 2021-09-20
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