A genome-wide approach to children's aggressive behavior: the EAGLE consortium

Pappa, Irene and St Pourcain, Beate and Benke, Kelly and Cavadino, Alana and Hakulinen, Christian and Nivard, Michel G. and Nolte, Ilja M. and Tiesler, Carla M. T. and Bakermans-Kranenburg, Marian J. and Davies, Gareth E. and Evans, David M. and Geoffroy, Marie-Claude and Grallert, Harald and Groen-Blokhuis, Maria M. and Hudziak, James J. and Kemp, John P. and Keltikangas-Järvinen, Liisa and McMahon, George and Mileva-Seitz, Viara R. and Motazedi, Ehsan and Power, Christine and Raitakari, Olli T. and Ring, Susan M. and Rivadeneira, Fernando and Rodriguez, Alina and Scheet, Paul A. and Seppälä, Ilkka and Snieder, Harold and Standl, Marie and Thiering, Elisabeth and Timpson, Nicholas J. and Veenstra, René and Velders, Fleur P. and Whitehouse, Andrew J. O. and Smith, George Davey and Heinrich, Joachim and Hypponen, Elina and Lehtimäki, Terho and Middeldorp, Christel M. and Oldehinkel, Albertine J. and Pennell, Craig E. and Boomsma, Dorret I. and Tiemeier, Henning (2015) A genome-wide approach to children's aggressive behavior: the EAGLE consortium. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 171 (5). ISSN 1552-4841

Full content URL: http://dx.doi.org/10.1002/ajmg.b.32333

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Item Type:Article
Item Status:Live Archive

Abstract

Individual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of aggressive behavior in children. We analyzed data from nine population-based studies and assessed aggressive behavior using well-validated parent-reported questionnaires. This is the largest sample exploring children's aggressive behavior to date (N = 18,988), with measures in two developmental stages (N = 15,668 early childhood and N = 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children's aggressive behavior based on genome-wide SNP information, using genome-wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi-Poisson regression approach, capturing the highly right-skewed distribution of aggressive behavior. Third, we performed meta-analyses of genome-wide associations for both the total age-mixed sample and the two developmental stages. Finally, we performed a gene-based test using the summary statistics of the total sample. GCTA quantified variance tagged by common SNPs (10–54%). The meta-analysis of the total sample identified one region in chromosome 2 (2p12) at near genome-wide significance (top SNP rs11126630, P = 5.30 × 10−8). The separate meta-analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene-based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. © 2015 Wiley Periodicals, Inc.

Additional Information:Special Issue: The Genetics of Aggression: Where Are We Now?
Keywords:Human genetics, JCOpen
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Social Science > School of Psychology
ID Code:22916
Deposited On:03 Aug 2016 09:34

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