@article{ref1,
title="Genetic association study of childhood aggression across raters, instruments, and age",
journal="Translational psychiatry",
year="2021",
author="Ip, Hill F. and Van der Laan, Camiel M. and Krapohl, Eva M. L. and Brikell, Isabell and Sánchez-Mora, Cristina and Nolte, Ilja M. and St Pourcain, Beate and Bolhuis, Koen and Palviainen, Teemu and Zafarmand, Hadi and Colodro-Conde, Lucia and Gordon, Scott and Zayats, Tetyana and Aliev, Fazil and Jiang, Chang and Wang, Carol A. and Saunders, Gretchen and Karhunen, Ville and Hammerschlag, Anke R. and Adkins, Daniel E. and Border, Richard and Peterson, Roseann E. and Prinz, Joseph A. and Thiering, Elisabeth and Seppälä, Ilkka and Vilor-Tejedor, Natàlia and Ahluwalia, Tarunveer S. and Day, Felix R. and Hottenga, Jouke-Jan and Allegrini, Andrea G. and Rimfeld, Kaili and Chen, Qi and Lu, Yi and Martin, Joanna and Soler Artigas, María and Rovira, Paula and Bosch, Rosa and Español, Gemma and Ramos Quiroga, Josep Antoni and Neumann, Alexander and Ensink, Judith and Grasby, Katrina and Morosoli, José J. and Tong, Xiaoran and Marrington, Shelby and Middeldorp, Christel and Scott, James G. and Vinkhuyzen, Anna and Shabalin, Andrey A. and Corley, Robin and Evans, Luke M. and Sugden, Karen and Alemany, Silvia and Sass, Lærke and Vinding, Rebecca and Ruth, Kate and Tyrrell, Jess and Davies, Gareth E. and Ehli, Erik A. and Hagenbeek, Fiona A. and De Zeeuw, Eveline and van Beijsterveldt, Toos C. E. M. and Larsson, Henrik and Snieder, Harold and Verhulst, Frank C. and Amin, Najaf and Whipp, Alyce M. and Korhonen, Tellervo and Vuoksimaa, Eero and Rose, Richard J. and Uitterlinden, Andre G. and Heath, Andrew C. and Madden, Pamela and Haavik, Jan and Harris, Jennifer R. and Helgeland, Øyvind and Johansson, Stefan and Knudsen, Gun Peggy S. and Njolstad, Pal Rasmus and Lü, Qing and Rodriguez, Alina and Henders, Anjali K. and Mamun, Abdullah and Najman, Jackob M. and Brown, Sandy and Hopfer, Christian Jean and Krauter, Kenneth and Reynolds, Chandra and Smolen, Andrew and Stallings, Michael and Wadsworth, Sally and Wall, Tamara L. and Silberg, Judy L. and Miller, Allison and Keltikangas-Järvinen, Liisa and Hakulinen, Christian and Pulkki-Råback, Laura and Havdahl, Alexandra and Magnus, Per and Raitakari, Olli T. and Perry, John R. B. and Llop, Sabrina and Lopez-Espinosa, Maria-Jose and Bønnelykke, Klaus and Bisgaard, Hans and Sunyer, Jordi and Lehtimäki, Terho and Arseneault, Louise and Standl, Marie and Heinrich, Joachim and Boden, Joseph and Pearson, John and Horwood, L. John and Kennedy, Martin and Poulton, Richie and Eaves, Lindon J. and Maes, Hermine H. and Hewitt, John and Copeland, William E. and Costello, Elizabeth J. and Williams, Gail M. and Wray, Naomi and Järvelin, Marjo-Riitta and McGue, Matt and Iacono, William and Caspi, Avshalom and Moffitt, Terrie E. and Whitehouse, Andrew and Pennell, Craig E. and Klump, Kelly L. and Burt, S. Alexandra and Dick, Danielle M. and Reichborn-Kjennerud, Ted and Martin, Nicholas G. and Medland, Sarah E. and Vrijkotte, Tanja and Kaprio, Jaakko and Tiemeier, Henning and Davey Smith, George and Hartman, Catharina A. and Oldehinkel, Albertine J. and Casas, Miquel and Ribasés, Marta and Lichtenstein, Paul and Lundström, Sebastian and Plomin, Robert and Bartels, Meike and Nivard, Michel G. and Boomsma, Dorret I.",
volume="11",
number="1",
pages="e413-e413",
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(overall)) 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 (r(g)) among rater-specific assessment of AGG ranged from r(g) = 0.46 between self- and teacher-assessment to r(g) = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r(g)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(g) = ~-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.<p /> <p>Language: en</p>",
language="en",
issn="2158-3188",
doi="10.1038/s41398-021-01480-x",
url="http://dx.doi.org/10.1038/s41398-021-01480-x"
}