Genetic association study of childhood aggression across raters, instruments, and age.
Creators: name: Ip, Hill F
name: Van Der Laan, Camiel M
name: Krapohl, Eva M L
name: Brikell, Isabell
name: Sánchez-Mora, Cristina
name: Nolte, Ilja M
name: St Pourcain, Beate
name: Bolhuis, Koen
name: Palviainen, Teemu
name: Zafarmand, Hadi
name: Colodro-Conde, Lucía
name: Gordon, Scott
name: Zayats, Tetyana
name: Aliev, Fazil
name: Jiang, Chang
name: Wang, Carol A
name: Saunders, Gretchen
name: Karhunen, Ville
name: Hammerschlag, Anke R
name: Adkins, Daniel E
name: Border, Richard
name: Peterson, Roseann E
name: Prinz, Joseph A
name: Thiering, Elisabeth
name: Seppälä, Ilkka
name: Vilor-Tejedor, Natàlia
name: Ahluwalia, Tarunveer S
name: Day, Felix R
name: Hottenga, Jouke-Jan
name: Allegrini, Andrea G
name: Rimfeld, Kaili
name: Chen, Qi
name: Lu, Yi
name: Martin, Joanna
name: Soler Artigas, María
name: Rovira, Paula
name: Bosch, Rosa
name: Español, Gemma
name: Ramos Quiroga, Josep Antoni
name: Neumann, Alexander
name: Ensink, Judith
name: Grasby, Katrina
name: Morosoli, José J
name: Tong, Xiaoran
name: Marrington, Shelby
name: Middeldorp, Christel
name: Scott, James G
name: Vinkhuyzen, Anna
name: Shabalin, Andrey A
name: Corley, Robin
name: Evans, Luke M
name: Sugden, Karen
name: Alemany, Silvia
name: Sass, Lærke
name: Vinding, Rebecca
name: Ruth, Kate
name: Tyrrell, Jess
name: Davies, Gareth E
name: Ehli, Erik A
name: Hagenbeek, Fiona A
name: De Zeeuw, Eveline
name: Van Beijsterveldt, Toos C E M
name: Larsson, Henrik
name: Snieder, Harold
name: Verhulst, Frank C
name: Amin, Najaf
name: Whipp, Alyce M
name: Korhonen, Tellervo
name: Vuoksimaa, Eero
name: Rose, Richard J
name: Uitterlinden, André G
name: Heath, Andrew C
name: Madden, Pamela
name: Haavik, Jan
name: Harris, Jennifer R
name: Helgeland, Øyvind
name: Johansson, Stefan
name: Knudsen, Gun Peggy S
name: Njolstad, Pal Rasmus
name: Lu, Qing
name: Rodriguez, Alina
name: Henders, Anjali K
name: Mamun, Abdullah
name: Najman, Jackob M
name: Brown, Sandy
name: Hopfer, Christian
name: Krauter, Kenneth
name: Reynolds, Chandra
name: Smolen, Andrew
name: Stallings, Michael
name: Wadsworth, Sally
name: Wall, Tamara L
name: Silberg, Judy L
name: Miller, Allison
name: Keltikangas-Järvinen, Liisa
name: Hakulinen, Christian
name: Pulkki-Råback, Laura
name: Havdahl, Alexandra
name: Magnus, Per
name: Raitakari, Olli T
name: Perry, John R B
name: Llop, Sabrina
name: Lopez-Espinosa, Maria-Jose
name: Bønnelykke, Klaus
name: Bisgaard, Hans
name: Sunyer, Jordi
name: Lehtimäki, Terho
name: Arseneault, Louise
name: Standl, Marie
name: Heinrich, Joachim
name: Boden, Joseph
name: Pearson, John
name: Horwood, L John
name: Kennedy, Martin
name: Poulton, Richie
name: Eaves, Lindon J
name: Maes, Hermine H
name: Hewitt, John
name: Copeland, William E
name: Costello, Elizabeth J
name: Williams, Gail M
name: Wray, Naomi
name: Järvelin, Marjo-Riitta
name: McGue, Matt
name: Iacono, William
name: Caspi, Avshalom
name: Moffitt, Terrie E
name: Whitehouse, Andrew
name: Pennell, Craig E
name: Klump, Kelly L
name: Burt, S Alexandra
name: Dick, Danielle M
name: Reichborn-Kjennerud, Ted
name: Martin, Nicholas G
name: Medland, Sarah E
name: Vrijkotte, Tanja
name: Kaprio, Jaakko
name: Tiemeier, Henning
name: Davey Smith, George
name: Hartman, Catharina A
name: Oldehinkel, Albertine J
name: Casas, Miquel
name: Ribasés, Marta
name: Lichtenstein, Paul
name: Lundström, Sebastian
name: Plomin, Robert
name: Bartels, Meike
name: Nivard, Michel G
name: Boomsma, Dorret I
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Humans
Retrospective Studies
Aggression
Mental Disorders
Adolescent
Child
Child, Preschool
Infant
Female
Genome-Wide Association Study
Genetic Association Studies

description: 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<sub>overall</sub>) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG<sub>overall</sub>. 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<sub>g</sub>) among rater-specific assessment of AGG ranged from r<sub>g</sub> = 0.46 between self- and teacher-assessment to r<sub>g</sub> = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r<sub>g</sub>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 [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r<sub>g</sub> = ~-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.