RT Journal Article
SR Electronic
T1 Genetic Association Study of Childhood Aggression across raters, instruments and age
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 854927
DO 10.1101/854927
A1 Hill F. Ip
A1 Camiel M. van der Laan
A1 Isabell Brikell
A1 Cristina Sánchez-Mora
A1 Ilja M. Nolte
A1 Beate St Pourcain
A1 Koen Bolhuis
A1 Teemu Palviainen
A1 Hadi Zafarmand
A1 Lucía Colodro-Conde
A1 Scott Gordon
A1 Tetyana Zayats
A1 Fazil Aliev
A1 Chang Jiang
A1 Carol A. Wang
A1 Gretchen Saunders
A1 Ville Karhunen
A1 Anke R. Hammerschlag
A1 Daniel E. Adkins
A1 Richard Border
A1 Roseann E. Peterson
A1 Joseph A. Prinz
A1 Elisabeth Thiering
A1 Ilkka Seppälä
A1 Natàlia Vilor-Tejedor
A1 Tarunveer S. Ahluwalia
A1 Felix R. Day
A1 Jouke-Jan Hottenga
A1 Andrea Allegrini
A1 Eva M. L. Krapohl
A1 Kaili Rimfeld
A1 Qi Chen
A1 Yi Lu
A1 Joanna Martin
A1 María Soler Artigas
A1 Paula Rovira
A1 Rosa Bosch
A1 Gemma Español
A1 Josep Antoni Ramos Quiroga
A1 Alexander Neumann
A1 Judith Ensink
A1 Katrina Grasby
A1 José J. Morosoli
A1 Xiaoran Tong
A1 Shelby Marrington
A1 Christel Middeldorp
A1 James G. Scott
A1 Anna Vinkhuyzen
A1 Andrey A. Shabalin
A1 Robin Corley
A1 Luke M. Evans
A1 Karen Sugden
A1 Silvia Alemany
A1 Lærke Sass
A1 Rebecca Vinding
A1 Kate Ruth
A1 Jess Tyrrell
A1 Gareth E. Davies
A1 Erik A. Ehli
A1 Fiona A. Hagenbeek
A1 Eveline De Zeeuw
A1 Toos C.E.M. Van Beijsterveldt
A1 Henrik Larsson
A1 Harold Snieder
A1 Frank C. Verhulst
A1 Najaf Amin
A1 Alyce M. Whipp
A1 Tellervo Korhonen
A1 Eero Vuoksimaa
A1 Richard J. Rose
A1 André G. Uitterlinden
A1 Andrew C. Heath
A1 Pamela Madden
A1 Jan Haavik
A1 Jennifer R. Harris
A1 Øyvind Helgeland
A1 Stefan Johansson
A1 Gun Peggy S. Knudsen
A1 Pal Rasmus Njolstad
A1 Qing Lu
A1 Alina Rodriguez
A1 Anjali K. Henders
A1 Abdullah Mamun
A1 Jackob M. Najman
A1 Sandy Brown
A1 Christian Hopfer
A1 Kenneth Krauter
A1 Chandra Reynolds
A1 Andrew Smolen
A1 Michael Stallings
A1 Sally Wadsworth
A1 Tamara Wall
A1 Judy L. Silberg
A1 Allison Miller
A1 Liisa Keltikangas-Järvinen
A1 Christian Hakulinen
A1 Laura Pulkki-Råback
A1 Alexandra Havdahl
A1 Per Magnus
A1 Olli T. Raitakari
A1 John R.B. Perry
A1 Sabrina Llop
A1 Maria-Jose Lopez-Espinosa
A1 Klaus Bønnelykke
A1 Hans Bisgaard
A1 Jordi Sunyer
A1 Terho Lehtimäki
A1 Louise Arseneault
A1 Marie Standl
A1 Joachim Heinrich
A1 Joseph Boden
A1 John Pearson
A1 John Horwood
A1 Martin Kennedy
A1 Richie Poulton
A1 Lindon J. Eaves
A1 Hermine H. Maes
A1 John Hewitt
A1 William E. Copeland
A1 Elizabeth J. Costello
A1 Gail M. Williams
A1 Naomi Wray
A1 Marjo-Riitta Järvelin
A1 Matt McGue
A1 William Iacono
A1 Avshalom Caspi
A1 Terrie E. Moffitt
A1 Andrew Whitehouse
A1 Craig E. Pennell
A1 Kelly L. Klump
A1 S. Alexandra Burt
A1 Danielle M. Dick
A1 Ted Reichborn-Kjennerud
A1 Nicholas G. Martin
A1 Sarah E. Medland
A1 Tanja Vrijkotte
A1 Jaakko Kaprio
A1 Henning Tiemeier
A1 George Davey Smith
A1 Catharina A. Hartman
A1 Albertine J. Oldehinkel
A1 Miquel Casas
A1 Marta Ribasés
A1 Paul Lichtenstein
A1 Sebastian Lundström
A1 Robert Plomin
A1 Meike Bartels
A1 Michel G. Nivard
A1 Dorret I. Boomsma
YR 2019
UL http://biorxiv.org/content/early/2019/11/29/854927.abstract
AB Childhood aggressive behavior (AGG) has a substantial heritability, with limited success in genome-wide association studies. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across age 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 rg’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 |rg|: 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 |rg|: 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.