Journal Article

A genome-wide association study of total child psychiatric problems scores

Natalia Vilor-Tejedor, Klaus Bønnelykke, Jari Lahti, Albertine J Oldehinkel, Hans Bisgaard, Liisa Keltikangas-Järvinen, Christel M Middeldorp, Carla M T Tiesler, Erik Pettersson, Yi Lu, Ang Zhou, Jouke-Jan Hottenga, Marinus H van IJzendoorn, Eva Krapohl, Ilja M Nolte, Carol Wang, Amanda Wills, Robert Plomin, Jaakko Kaprio, Tarunveer S Ahluwalia, Elina Hyppönen, Henning Tiemeier, Gareth E Davies, Beben Benyamin, Lærke Sass, Harold Snieder, Catharina E M van Beijsterveldt, Olli T Raitakari, Jakob Stokholm, Gail M Williams, Ville Karhunen, Anjali K Henders, Alina Rodriguez, Tellervo Korhonen, Beate St Pourcain, Marian J Bakermans-Kranenburg, Alexander Neumann, Craig Pennell, Catharina A Hartman, Joachim Heinrich, Marie Standl, Peter J van der Most, Meike Bartels, Chris Power, Marius Lahti-Pulkkinen, Anke R Hammerschlag, Dorret I Boomsma, Jackob M Najman, Ilkka Seppälä, Silvia Alemany, Quinta Helmer, Anna Suarez, John Hewitt, Christian Hakulinen, Irene Pappa, Andrew Whitehouse, Kaili Rimfeld, Katri Räikkönen, Jordi Sunyer, Teemu Palviainen, Terho Lehtimäki

2022

Overview

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.

• Publisher: Public Library of Science (PLoS)