Genetic association study of childhood aggression across raters, instruments, and age
Ip, Hill F. (Vrije Universiteit Amsterdam)
van der Laan, Camiel M. (Netherlands Institute for the Study of Crime and Law Enforcement)
Krapohl, Eva M. L. (King's College London)
Brikell, Isabell (Karolinska Institutet (Estocolm, Suècia))
Sánchez-Mora, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nolte, Ilja M. (University of Groningen)
Pourcain, Beate St (Radboud University)
Bolhuis, Koen (Erasmus University Medical Center)
Palviainen, Teemu (University of Helsinki)
Zafarmand, Hadi (University of Amsterdam)
Colodro-Conde, Lucía (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Gordon, Scott D (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Zayats, Tetyana (Stanley Center for Psychiatric Research)
Aliev, Fazil (Karabuk University)
Jiang, Chang (University of Florida)
Wang, Carol A. (The University of Newcastle)
Saunders, Gretchen (University of Minnesota)
Karhunen, Ville (Imperial College London)
Hammerschlag, Anke R. (Amsterdam Public Health Research Institute)
Adkins, Daniel E. (University of Utah)
Border, Richard (University of Colorado Boulder)
Peterson, Roseann E. (Virginia Commonwealth University)
Prinz, Joseph A. (Duke University)
Thiering, Elisabeth (Ludwig-Maximilians-University of Munich)
Seppälä, Ilkka (Tampere University)
Vilor-Tejedor, Natàlia (Fundació Pasqual Maragall (FPM))
Ahluwalia, Tarunveer Singh (Steno Diabetes Center Copenhagen)
Day, Felix R. (University of Cambridge School of Clinical Medicine)
Hottenga, Jouke Jan (Vrije Universiteit Amsterdam)
Allegrini, Andrea G. (King's College London)
Rimfeld, Kaili (King's College London)
Chen, Qi (Karolinska Institutet (Estocolm, Suècia))
Lu, Yi (Karolinska Institutet (Estocolm, Suècia))
Martin, Joanna (Cardiff University)
Soler Artigas, María (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rovira, Paula (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bosch, Rosa (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Español-Martín, Gemma (Hospital Universitari Vall d'Hebron)
Ramos-Quiroga, Josep Antoni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Neumann, Alexander (Jewish General Hospital)
Ensink, Judith (De Bascule, Academic Centre for Child and Adolescent Psychiatry)
Grasby, Katrina (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Morosoli, José J. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Tong, Xiaoran (University of Florida)
Marrington, Shelby (The University of Queensland)
Middeldorp, Christel (Children's Health Queensland Hospital)
Scott, James G. (Queensland Centre for Mental Health Research)
Vinkhuyzen, Anna (University of Queensland)
Shabalin, Andrey A. (University of Utah)
Corley, Robin (University of Colorado Boulder)
Evans, Luke M. (University of Colorado Boulder)
Sugden, Karen (Duke University)
Alemany, Sílvia (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Sass, Lærke (University of Copenhagen)
Vinding, Rebecca (University of Copenhagen)
Ruth, Kate (University of Exeter Medical School)
Tyrrell, Jess (University of Exeter Medical School)
Davies, Gareth E. (Avera Institute for Human Genetics)
Ehli, Erik A. (Avera Institute for Human Genetics)
Hagenbeek, Fiona A. (Vrije Universiteit Amsterdam)
De Zeeuw, Eveline (Vrije Universiteit Amsterdam)
Van Beijsterveldt, Toos C.E.M. (Vrije Universiteit Amsterdam)
Larsson, Henrik (Orebro University)
Snieder, Harold (University of Groningen)
Verhulst, Frank C. (Copenhagen University Hospital)
Amin, Najaf (Erasmus University Medical Center)
Whipp, Alyce M. (University of Helsinki)
Korhonen, Tellervo (University of Helsinki)
Vuoksimaa, Eero (University of Helsinki)
Rose, Richard J. (Indiana University)
Uitterlinden, André G. (Netherlands Genomics Initiative (NGI))
Heath, Andrew C. (Washington University)
Madden, Pamela (Washington University)
Haavik, Jan (Haukeland University Hospital (Bergen, Noruega))
Harris, Jennifer R. (The Norwegian Institute of Public Health)
Helgeland, Øyvind (The Norwegian Institute of Public Health)
Johansson, Stefan E (University of Bergen)
Knudsen, Gun Peggy S. (The Norwegian Institute of Public Health)
Njolstad, Pal Rasmus (University of Bergen)
Lu, Qing (University of Florida)
Rodriguez, Alina (University of Lincoln)
Henders, Anjali K. (University of Queensland)
Mamun, Abdullah (University of Queensland)
Najman, Jackob M. (The University of Queensland)
Brown, Sandy (University of California)
Hopfer, Christian (University of Colorado School of Medicine)
Krauter, Kenneth (University of Colorado Boulder)
Reynolds, Chandra (University of California Riverside)
Smolen, Andrew (University of Colorado Boulder)
Stallings, Michael (University of Colorado Boulder)
Wadsworth, Sally (University of Colorado Boulder)
Wall, Tamara L. (University of California)
Silberg, Judy L. (Virginia Commonwealth University)
Miller, Allison (University of Otago Christchurch)
Keltikangas-Järvinen, Liisa (University of Helsinki)
Hakulinen, Christian (University of Helsinki)
Pulkki-Råback, Laura (University of Helsinki)
Havdahl, Alexandra (Norwegian Institute of Public Health)
Magnus, Per (Norwegian Institute of Public Health)
Raitakari, Olli T. (Turku University Hospital)
Perry, John R. B. (University of Cambridge School of Clinical Medicine)
Llop, Sabrina (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Lopez-Espinosa, Maria-Jose (Universitat de València)
Bønnelykke, Klaus (University of Copenhagen)
Bisgaard, Hans (University of Copenhagen)
Sunyer Deu, Jordi (Institut Hospital del Mar d'Investigacions Mèdiques)
Lehtimäki, Terho (Tampere University)
Arseneault, Louise (Duke University School of Medicine)
Standl, Marie (Helmholtz Zentrum München)
Heinrich, Joachim (University of Melbourne)
Boden, Joseph (University of Otago Christchurch)
Pearson, John (University of Otago Christchurch)
Horwood, L. John (University of Otago Christchurch)
Kennedy, Martin (University of Otago Christchurch)
Poulton, Richie (University of Otago)
Eaves, Lindon J. (Virginia Institute for Psychiatric and Behavioral Genetics)
Maes, Hermine H. (Virginia Commonwealth University)
Hewitt, John (University of Colorado Boulder)
Copeland, William E. (University of Vermont)
Costello, Elizabeth J. (Duke University)
Williams, Gail M. (The University of Queensland)
Wray, Naomi R (University of Queensland)
Järvelin, Marjo-Riitta (University of Oulu)
McGue, Matt (University of Minnesota)
Iacono, William (University of Minnesota)
Caspi, Avshalom (King's College London)
Moffitt, Terrie E. (King's College London)
Whitehouse, Andrew (The University of Western Australia)
Pennell, Craig E. (The University of Newcastle)
Klump, Kelly L. (Michigan State University)
Burt, S. Alexandra (Michigan State University)
Dick, Danielle M. (Virginia Commonwealth University)
Reichborn-Kjennerud, Ted (University of Oslo)
Martin, Nicholas G (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Medland, Sarah Elizabeth (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Vrijkotte, Tanja (University of Amsterdam)
Kaprio, Jaakko (University of Helsinki)
Tiemeier, Henning (Harvard TH Chan School of Public Health)
Smith, George Davey (University of Bristol)
Hartman, Catharina A. (University of Groningen)
Oldehinkel, Albertine J (University of Groningen)
Casas Brugué, Miquel (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Ribasés Haro, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lichtenstein, Paul (Karolinska Institutet (Estocolm, Suècia))
Lundström, Sebastian (University of Gothenburg)
Plomin, Robert (King's College London)
Bartels, Meike (Amsterdam Public Health Research Institute)
Nivard, Michel G. (Vrije Universiteit Amsterdam)
Boomsma, Dorret I (Amsterdam Public Health Research Institute)

Date:	2021
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 (AGG) was 3. 31% (SE = 0. 0038). We found no genome-wide significant SNPs for AGG. 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 (r ) among rater-specific assessment of AGG ranged from r = 0. 46 between self- and teacher-assessment to r = 0. 81 between mother- and teacher-assessment. We obtained moderate-to-strong r s 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 : 0. 19-1. 00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r = ~−0. 5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range : 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Human behaviour ; Genomics
Published in:	Translational psychiatry, Vol. 11 (july 2021) , ISSN 2158-3188

DOI: 10.1038/s41398-021-01480-x
PMID: 34330890

9 p, 2.7 MB

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