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-Tejedor; Carla 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

doi:10.1371/journal.pone.0273116

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-Tejedor

Carla 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 Journal › Article › Academic › peer-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 language	English
Article number	e0273116
Pages (from-to)	1-23
Number of pages	23
Journal	PLoS ONE
Volume	17
Issue number	8
Early online date	22 Aug 2022
DOIs	https://doi.org/10.1371/journal.pone.0273116
Publication status	Published - 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.

Funding

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.

Funders	Funder number
ZonMw
NWO-VICI
Dutch Ministry of Education, Culture, and Science
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	024.001.003, 480-01-006
Horizon 2020 Framework Programme	681466, 633595
National Health and Medical Research Council	1077966, 572613
European Commission	201413
Wellcome Trust	095219, 076113
UK Research and Innovation	G0000934, ES/M001660/1

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Neumann, A., Nolte, I. M., Pappa, I., Ahluwalia, T. S., Pettersson, E., Rodriguez, A., Whitehouse, A., van Beijsterveldt, C. E. M., Benyamin, B., Hammerschlag, A. R., Helmer, Q., Karhunen, V., Krapohl, E., Lu, Y., van der Most, P. J., Palviainen, T., St Pourcain, B., Seppälä, I., Suarez, A., ... Tiemeier, H. (2022). A genome-wide association study of total child psychiatric problems scores. PLoS ONE, 17(8), 1-23. Article e0273116. https://doi.org/10.1371/journal.pone.0273116

@article{4b8194ed802140389101b6ae2418181d,

title = "A genome-wide association study of total child psychiatric problems scores",

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.",

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

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{\textquoteright}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: {\textcopyright} 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.",

year = "2022",

month = aug,

doi = "10.1371/journal.pone.0273116",

language = "English",

volume = "17",

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Neumann, A, Nolte, IM, Pappa, I, Ahluwalia, TS, Pettersson, E, Rodriguez, A, Whitehouse, A, van Beijsterveldt, CEM, Benyamin, B, Hammerschlag, AR, Helmer, Q, Karhunen, V, Krapohl, E, Lu, Y, van der Most, PJ, Palviainen, T, St Pourcain, B, Seppälä, I, Suarez, A, Vilor-Tejedor, N, Tiesler, CMT, Wang, C, Wills, A, Zhou, A, Alemany, S, Bisgaard, H, Bønnelykke, K, Davies, GE, Hakulinen, C, Henders, AK, Hyppönen, E, Stokholm, J, Bartels, M, Hottenga, JJ, Heinrich, J, Hewitt, J, Keltikangas-Järvinen, L, Korhonen, T, Kaprio, J, Lahti, J, Lahti-Pulkkinen, M, Lehtimäki, T, Middeldorp, CM, Najman, JM, Pennell, C, Power, C, Oldehinkel, AJ, Plomin, R, Räikkönen, K, Raitakari, OT, Rimfeld, K, Sass, L, Snieder, H, Standl, M, Sunyer, J, Williams, GM, Bakermans-Kranenburg, MJ, Boomsma, DI, van IJzendoorn, MH, Hartman, CA & Tiemeier, H 2022, 'A genome-wide association study of total child psychiatric problems scores', PLoS ONE, vol. 17, no. 8, e0273116, pp. 1-23. https://doi.org/10.1371/journal.pone.0273116

TY - JOUR

T1 - A genome-wide association study of total child psychiatric problems scores

AU - Neumann, Alexander

AU - Nolte, Ilja M.

AU - Pappa, Irene

AU - Ahluwalia, Tarunveer S.

AU - Pettersson, Erik

AU - Rodriguez, Alina

AU - Whitehouse, Andrew

AU - van Beijsterveldt, Catharina E.M.

AU - Benyamin, Beben

AU - Hammerschlag, Anke R.

AU - Helmer, Quinta

AU - Karhunen, Ville

AU - Krapohl, Eva

AU - Lu, Yi

AU - van der Most, Peter J.

AU - Palviainen, Teemu

AU - St Pourcain, Beate

AU - Seppälä, Ilkka

AU - Suarez, Anna

AU - Vilor-Tejedor, Natalia

AU - Tiesler, Carla M.T.

AU - Wang, Carol

AU - Wills, Amanda

AU - Zhou, Ang

AU - Alemany, Silvia

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

AU - Davies, Gareth E.

AU - Hakulinen, Christian

AU - Henders, Anjali K.

AU - Hyppönen, Elina

AU - Stokholm, Jakob

AU - Bartels, Meike

AU - Hottenga, Jouke Jan

AU - Heinrich, Joachim

AU - Hewitt, John

AU - Keltikangas-Järvinen, Liisa

AU - Korhonen, Tellervo

AU - Kaprio, Jaakko

AU - Lahti, Jari

AU - Lahti-Pulkkinen, Marius

AU - Lehtimäki, Terho

AU - Middeldorp, Christel M.

AU - Najman, Jackob M.

AU - Pennell, Craig

AU - Power, Chris

AU - Oldehinkel, Albertine J.

AU - Plomin, Robert

AU - Räikkönen, Katri

AU - Raitakari, Olli T.

AU - Rimfeld, Kaili

AU - Sass, Lærke

AU - Snieder, Harold

AU - Standl, Marie

AU - Sunyer, Jordi

AU - Williams, Gail M.

AU - Bakermans-Kranenburg, Marian J.

AU - Boomsma, Dorret I.

AU - van IJzendoorn, Marinus H.

AU - Hartman, Catharina A.

AU - Tiemeier, Henning

N1 - 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.

PY - 2022/8

Y1 - 2022/8

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85136217109

UR - https://www.scopus.com/pages/publications/85136217109#tab=citedBy

U2 - 10.1371/journal.pone.0273116

DO - 10.1371/journal.pone.0273116

M3 - Article

C2 - 35994476

AN - SCOPUS:85136217109

SN - 1932-6203

VL - 17

SP - 1

EP - 23

JO - PLoS ONE

JF - PLoS ONE

IS - 8

M1 - e0273116

ER -

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

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