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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere0273116
JournalPLoS ONE
Volume17
Issue number8 August
DOIs
Publication statusPublished - 22 Aug 2022

Bibliographical note

Funding Information:
A. Neumann and H. Tiemeier are supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development). The work of H. Tiemeier is further supported by a European Union’s Horizon 2020 research and innovation program (Contract grant number: 633595, DynaHealth) and a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). https://www.nwo.nl/The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
Copyright: © 2022 Neumann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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